Identifying New Therapeutic Targets in Epithelial Ovarian Cancer

Identifying New Therapeutic Targets in Epithelial Ovarian Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Identifying New Therapeutic Targets in Epithelial Ovarian Cancer Alessia Piermattei, Roberto De Luca, Frederik Peissert, Louis Plüss, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4490240/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Ovarian cancer is a significant health concern, necessitating the identification of potential diagnostic markers and novel therapeutic targets. This study presents, to the best of our knowledge, the first comparative immunohistochemical analysis of five tumor markers, namely the extra-domains A and B of fibronectin, fibroblast activation protein, carcinoembryonic antigen, and MUC16 in human epithelial ovarian cancer tissue samples. Methods Formalin-fixed paraffin-embedded human ovarian tissue sections were stained using previously validated antibodies to assess the percentage and intensity of marker expressions. Results Our results indicate a similar stromal pattern of expression for fibroblast activation protein, extra-domains A, and extra-domains B, with extra-domains A exhibiting the most intense staining. MUC16 was abundantly expressed on tumor cells of high-grade serous carcinoma samples, while carcinoembryonic antigen was not detected in this indication. Subsequent staining revealed that carcinoembryonic antigen was highly expressed on mucinous ovarian cancer specimens. With respect to clinical features, MUC16 and extra-domains A were found to be highly expressed in the most challenging scenarios namely platinum-resistant (100% and 50% respectively) and BRCA WT (75% and 45% respectively) patients. Conclusions The findings of this study highlight that MUC16, extra-domains B, and extra-domains A are attractive targets for the treatment of serous ovarian carcinoma, while carcinoembryonic antigen could be exploited for mucinous ovarian cancer. Clinical investigations are warranted to validate the potential of antibody-based therapies targeting these antigens in the context of ovarian cancer. ovarian cancer Extra domain A of fibronectin Extra domain B of fibronectin Fibroblast activation protein Carcinoembryonic Antigen MUC16 therapeutic antibodies vascular targeting targeted therapy Figures Figure 1 Figure 2 Background Epithelial ovarian carcinoma (EOC) is the leading cause of death among all gynecological cancers in developed countries, mainly due to the lack of early diagnosis coupled with the frequent acquisition of resistance to available treatments ( 1 ). In the past decade, the therapeutic landscape for EOC has witnessed a significant evolution. Initially centered around debulking surgery and platinum-based chemotherapy, the treatment algorithm has since been enriched by the integration of targeted therapies such as vascular endothelial growth factor (VEGF) and Poly (ADP-ribose) polymerase (PARP) inhibitors ( 2 ). The optimal positioning of current available therapies within the EOC treatment algorithm remains challenging. Indirect and not exhaustive biomarkers for platinum-based chemotherapy and PARP inhibitors sensitivity in high-grade serous OC (HGSOC) patients, are BRCA1/2 genes mutations and homologous recombination deficiency (HR-d). Patients harboring these genomic alterations have a defective DNA double-strand break repair mechanism, making chemotherapy cytotoxic anti-cancer activity more effective. Yet, chemotherapy does not discriminate healthy from malignant proliferating cells, leading to a high toxicity profile. No predictive biomarkers of response to the VEGF inhibitor Bevacizumab are currently available and the overall survival benefit that this drug promotes remains questionable in many cancers( 3 )( 4 ) . Furthermore, the emergence of de novo or acquired resistance to these novel therapies is emerging as relevant unmet need in recurrent settings, with no available tumor biomarkers for such challenges. These biomarkers could be exploited for the selective delivery of bioactive payloads to the site of disease. Approximately 20% of EOC patients that currently do not respond to any standard therapy, may benefit from the development of such innovative treatment approaches ( 5 ); ( 6 ); ( 7 ). The alternatively spliced extra-domain B (EDB) and A (EDA) of fibronectin are among the best-characterized markers of angiogenesis. Both domains are virtually undetectable in normal adult tissues (with the exception of the endometrium in the proliferative phase and some vessels of the ovaries) but are strongly expressed in most aggressive cancers, with a prominent vascular and stromal pattern of expression ( 8 ); ( 9 ): ( 10 ). The fully human monoclonal antibodies L19 and F8 have been isolated encoded combinatorial libraries and are directed against the alternatively-spliced EDB and EDA domains of fibronectin, respectively ( 11 ) ( 12 ). These antibodies have been shown to selectively localize around tumor neo-vasculature structures in animal cancer models and in patients, making them valuable tools for cancer research and potential therapeutic applications. Fibroblast Activation Protein (FAP) is a transmembrane serine protease rarely expressed in healthy adult tissues but abundantly expressed on the surface of cancer-associated fibroblasts (CAFs) and in the stroma of pathological conditions such as cancer. The antigen has garnered significant attention as the 'next billion-dollar nuclear theranostics target', based on the successful imaging data generated in over 28 different tumor types in patients using radiolabeled FAP-targeting ligands ( 13 ). Carcinoembryonic antigen (CEA) is a well-validated cell surface antigen primarily associated with metastatic colorectal cancer (mCRC). Additionally, it is expressed in breast, liver, lung, stomach, pancreatic, ovarian cancers and other malignancies. Structurally, CEA is a GPI-anchored membrane protein comprising seven Ig-like domains. In healthy organs, CEA expression remains confined to the apical surface of mature enterocytes, rendering it virtually inaccessible to circulating antibodies. However, in malignant cells, the polarity of CEA expression is disrupted, leading to its exposure to the vasculature and lymphatic system. The immunohistochemical staining of CEA plays an essential role in differential diagnosis of Mucinous ovarian cancer (MOC) from other possible subtypes of EOC. The fully human monoclonal antibody F4 has been isolated from a phage display library and has been shown to selectively localize in CEA-positive tumors in preclinical models (( 14 ). MUC16, commonly known as CA-125, represents a promising and valuable antigen for targeted immunotherapy for the treatment of OC. This antigen has emerged as a focal point of interest in cancer research due to its crucial role in disease pathogenesis and progression. MUC16 overexpression has been extensively linked to various detrimental cellular processes. Elevated levels of the antigen have been associated with enhanced cell proliferation, facilitating the uncontrolled growth of cancer cells. Furthermore, it has been implicated in promoting the migration and invasion of tumor cells, leading to the metastatic spread of the disease ( 15 ). In this article, we present the results of a comparative immunohistochemical evaluation of five validated antibodies F8 ( 11 ), L19 ( 12 ), anti-FAP (Abcam), F4 ( 14 )and CA 125 Clone M11 (Dako Omnis), specific to EDA, EDB, FAP, CEA, and MUC16, respectively, on selected EOC patient samples. The tested antibodies represent suitable delivery vehicles for various anti-cancer payloads (e.g., cytokines or cytotoxics) for the treatment of EOC. Methods Patients and study design This is a no-profit, observational, retrospective study, approved by the Institutional Ethics Committee (ID 6144). The inclusion criteria were defined as follows: patients with histological diagnosis of EOC, available formalin-fixed, paraffin-embedded (FFPE) tissues at diagnosis (baseline), updated clinical information (baseline information, pathological and molecular features when applicable, medical and surgical treatments, follow-up) and available signed informed consent. Patients were excluded in case of non-epithelial histology and less than 30% of tumor cells in the FPPE specimen. For eligible patients, clinical data were retrieved from their medical records. An immunohistochemistry (IHC) analysis with a panel of antibodies for the immuno-oncology targets EDA, EDB, FAP, CEA and MUC16 was performed on one representative tissue sample from a tumor block of all cases at baseline and, when available, at relapse. Pseudo-anonymized data were collected and managed using REDCap electronic data capture tools hosted at https://redcap-irccs.policlinicogemelli.it/ ( 16 ). All data were processed in compliance with European Regulation on the Privacy of data (UE 2016/679). Data analysis A total number of 60 samples was estimated based on the intensity and expression of the above reported antibodies on EOC samples according to Human Protein Atlas ( https://www.proteinatlas.org/ ; L19 antibody 58%, F8 antibody: 92%, anti-FAP antibody: 30%, anti-CEA antibody: 10% and anti-MUC16 antibody: 100%). Continuous variables were summarized as medians and interquartile ranges and differences between variables were analyzed by using the Mann-Whitney U test. Categorical variables were used to express the number of cases and percentages (%). Associations have been assessed by the chi-square or Fisher exact test, used as appropriate according to the expected frequency in each cell and differences in mean values were examined through the Student’s t-test. Median follow up was calculated with the inverse Kaplan-Meier technique ( 17 ). Survival outcomes were presented in terms of both disease-free survival (DFS) and overall survival (OS). DFS was defined as the time that elapsed from the first pathological diagnosis to recurrence or last follow-up, whereas OS was defined as the time from the first pathological diagnosis to death or last follow-up. Median OS and DFS were estimated with the Kaplan–Meier product limit method ( 18 ) and were presented with a 95% confidence interval. All statistical tests used a two-tailed α of 0.05. All analyses were performed using SPSS version 24.0. Sample processing The FFPE tissue blocks were collected and cut into 3-µm thick sections. Haematoxylin and eosin (H&E) stained sections from FFPE were double-blind reviewed by two expert pathologists. IHC staining of FFPE tissues was performed with the F8, L19 and F4 antibodies (Philogen), anti-FAP (Abcam) and CA 125 Clone M11 (Dako Omnis), followed by appropriate secondary monoclonal rabbit anti-human antibodies using the BOND Polymer Refine Detection on the Bond III automated immunostainer (Leica Microsystems, Bannockburn, IL). A negative and positive control staining versus reactivity with the mAbs was performed in each series. The F8, L19, anti-FAP and anti-MUC16 staining was evaluated based on the intensity signal (absent, 0; weak, 1+; moderate, 2+; strong, 3+) and the percentage of positive immunoreactive cells for the respective target (EDA, EDB, FAP, and MUC16, respectively). The results of CEA immunohistochemical staining were interpreted based on the localization pattern of the antigen in MOC tissues: (0; negative/absent staining), (1; staining restricted to the apical membrane: apical-type), (2; staining on the apical/basolateral cellular membrane), (3; staining on the apical and luminal). The antibody clones did not have the same affinity towards their cognate antigen, so they were used at different concentrations. Results Between March 2016 and March 2024, a total of 47 patients with EOC were retrospectively enrolled. Baseline samples were accessible for all patients, with 13 of them additionally having matched biopsy samples taken at the time of relapse. Patients with HGSOC, CCC (clear-cell carcinoma) and low-grade serous ovarian cancer (LGOC) were further categorized based on clinico-molecular characteristics: Group A: Patients with wild-type (WT) BRCA1/2 genes (n=20) Group B: Patients with mutant BRCA1/2 genes (n=17) Group C: Patients who experienced recurrence with a platinum-free interval (PFI) of less than 6 months (n=4) Group D: Patients who experienced recurrence with a platinum-free interval (PFI) of more than 6 months (n=25) Group E: Patients who did not experience relapse (n=8) Group F: Patients with matched baseline and recurrence samples (n=13) MOC patients were considered separately, and tested only for CEA (group G, n=10) ( Figure 1 ). Clinico-pathological characteristics of enrolled patients are summarized in Table 1 A and B ; Additional Table 1 shows the ones of matched sample at recurrence. In detail, the IHC analysis using the F8, L19, anti-FAP, CEA and anti-MUC16 antibodies was performed on 37 ovary primary tumors, 12 peritoneal and one vaginal nodule metastasis. In addition, on the MOC samples, the anti-CEA staining was performed. Table 1A . Clinical HGSOC, CCC, LGSC patients’ characteristics Characteristic All cases n=37 BRCA status Disease status Group A: Wild type n=20 Group B: Mutated n=17 Group C: PFI < 6 months n=4 Group D: PFI ≥ 6 months n=25 Group E: Absence of recurrence n=8 Age at diagnosis, years 52 (33-73) 55.5 (33-73) 51 (39-64) 54 (47-57) 49 (37-73) 58.5 (33-62) Body mass index, kg/m 2 24.1 (18.2-34.2) 24.1 (18.2-32) 24.1 (18.5-34.2) 23.6 (19.2-30.8) 24.8 (18.2-34.2) 23.1 (18.5-34.2) Body mass index classification Underweight 2 (5.4) 2 (10.0) 0 (0.0) 0 (0.0) 2 (8.0) 0 (0.0) Normal weight 19 (51.4) 10 (50.0) 9 (52.9) 3 (75.0) 11 (44.0) 5 (62.5) Overweight 11 (29.7) 6 (30.0) 5 (29.4) 0 (0.0) 10 (40.0) 1 (12.5) Obese 5 (13.5) 2 (10.0) 3 (17.6) 1 (25.0) 2 (8.0) 2 (25.0) Post menopause 18 (50.0) 10 (52.6) 8 (47.1) 3 (75.0) 10 (40.0) 5 (71.4) Symptoms at diagnosis No symptoms 6 (16.2) 2 (10.0) 4 (23.5) 1 (25.0) 3 (12.0) 2 (25.0) Abdominal pain 14 (37.8) 10 (50.0) 4 (23.5) 2 (50.0) 10 (40.0) 2 (25.0) Abdominal distension 8 (21.6) 5 (25.0) 3 (17.6) 1 (25.0) 7 (28.0) 0 (0.0) Blood loss 3 (8.1) 1 (5.0) 2 (11.8) 0 (0.0) 1 (4.0) 2 (25.0) Other 6 (16.2) 2 (10.0) 4 (23.5) 0 (0.0) 4 (16.0) 2 (25.0) CA-125 at diagnosis 418.5 (5-17730) 768.5 (5-17730) 301.9 (55.7-2272) 6652 (95.8-17730) 462.5 (5-5814.4) 177.3 (55.7-13110) ECOG 0 27 (73.0) 13 (65.0) 14 (82.4) 3 (75.0) 18 (72.0) 6 (75.0) 1 10 (27.0) 7 (35.0) 3 (17.6) 1 (25.0) 7 (28.0) 2 (25.0) Histotype Serous high-grade carcinoma 35 (94.6) 19 (95.0) 16 (94.1) 4 (100.0) 24 (96.0) 7 (87.5) Serous low-grade carcinoma 1 (2.7) 0 (0.0) 1 (5.9) 0 (0.0) 1 (4.0) 0 (0.0) Clear cells carcinoma 1 (2.7) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) Grading Not applicable 1 (2.7) 1 (5.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) 1 1 (2.7) 0 (0.0) 1 (5.9) 0 (0.0) 1 (4.0) 0 (0.0) 3 35 (94.6) 19 (95.0) 16 (94.1) 4 (100.0) 24 (96.0) 7 (87.5) FIGO stage IIIA1 2 (5.4) 2 (10.0) 0 (0.0) 1 (25.0) 1 (4.0) 0 (0.0) IIIA2 2 (5.4) 1 (5.0) 1 (5.9) 0 (0.0) 1 (4.0) 1 (12.5) IIIB 2 (5.4) 1 (5.0) 1 (5.9) 0 (0.0) 1 (4.0) 1 (12.5) IIIC 22 (59.5) 11 (55.0) 11 (64.7) 1 (25.0) 17 (68.0) 4 (50.0) IVA 1 (2.7) 0 (0.0) 1 (5.9) 1 (25.0) 0 (0.0) 0 (0.0) IVB 8 (21.6) 5 (25.0) 3 (17.6) 1 (25.0) 5 (20.0) 2 (25.0) Clinical HGSOC, CCC, LGSC patients’ characteristics Table 1 B Clinical MOC patients’ characteristics Characteristics Group G= Mucinous carcinoma n=10 Age at diagnosis, years 46.5 (34-75) Body mass index, kg/m 2 22.9 (20.5-37.2) Body mass index classification Underweight 0 (0.0) Normal weight 7 (70.0) Overweight 0 (0.0) Obese 3 (30.0) Post menopause 3 (30.0) Symptoms at diagnosis No symptoms 3 (30.0) Abdominal pain 4 (40.0) Abdominal distension 0 (0.0) Blood loss 1 (10.0) Other 2 (20.0) CA-125 at diagnosis 65.7 (12.6-383) ECOG 0 7 (70.0) 1 3 (30.0) Histotype Mucinous 10 (100.0) Grading 1 0 (0.0) 2 6 (60.0) 3 4 (40.0) FIGO stage IA 6 (60.0) IC1 1 (10.0) IC2 2 (20.0) IIIC 1 (10.0) Results are presented as n (%) or median (min-max) as appropriate. BRCA: BReast CAncer gene. PFI: Platinum Free Interval. ECOG: Eastern Cooperative Oncology Group. FIGO: international federation of gynaecology and obstetrics. No relevant difference in baseline clinical characteristics was found across the groups. The vast majority of patients was diagnosed with HGSOC. No relevant differences in terms of age were observed between the groups. Data on surgery, treatment, and survival characteristics are reported in Table 2 A and B . All patients underwent primary debulking surgery (PDS) and an absent residual tumor was achieved in 94.4% of cases. All patients received platinum-based chemotherapy as first-line treatment, achieving a favorable biochemical response demonstrated by a decrease in CA-125 levels to within normal range. The significant majority (95.5%) of patients received bevacizumab both during chemotherapy and as part of maintenance. In group B, two patients received PARP inhibitors in first-line. Of all enrolled patients, 75.6% experienced recurrence, with the disease primarily localized in the peritoneum or lymph nodes. Table 2 A Surgical treatment and survival characteristics data of HGSOC, CCC, LGSC patients Characteristic All cases n=37 BRCA status Disease status Group A: Wild type n=20 Group B: Mutated n=17 Group C: PFI < 6 months n=4 Group D: PFI ≥ 6 months n=25 Group E: Absence of recurrence n=8 ASA 1 8 (29.6) 4 (23.5) 4 (40.0) 0 (0.0) 4 (25.0) 4 (57.1) 2 18 (66.7) 12 (70.6) 6 (60.0) 4 (100.0) 12 (75.0) 2 (28.6) 3 1 (3.7) 1 (5.9) 0 (0.0) 0 (0.0) 0 (0.0) 1 (14.3) Primary debulking surgery 37 (100.0) 20 (100.0) 17 (100.0) 4 (100.0) 25 (100.0) 8 (100.0) Intraperitoneal chemotherapy 2 (5.4) 0 (0.0) 2 (11.8) 0 (0.0) 2 (8.0) 0 (0.0) Aletti Score 1 2 (5.4) 1 (5.0) 1 (5.9) 0 (0.0) 1 (4.0) 1 (12.5) 2 15 (40.5) 7 (35.0) 8 (47.1) 1 (25.0) 9 (36.0) 5 (62.5) 3 20 (54.1) 12 (60.0) 8 (47.1) 3 (75.0) 15 (60.0) 2 (25.0) Residual tumor Absent 34 (94.4) 18 (94.7) 16 (94.1) 4 (100.0) 22 (91.7) 8 (100.0) < = 0.5 cm 2 (5.6) 1 (5.3) 1 (5.9) 0 (0.0) 2 (8.3) 0 (0.0) Operating 380 (180-660) 370 (240-660) 385 (180-600) 402.5 (270-660) 390 (180-600) 270 (240-491) Chemotherapy No 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Yes 37 (100.0) 20 (100.0) 17 (100.0) 4 (100.0) 25 (100.0) 8 (100.0) Chemotherapy regimen Carboplatin taxol 16 (43.2) 8 (40.0) 8 (47.1) 1 (25.0) 10 (40.0) 5 (62.5) Carboplatin taxol bevacizumab 20 (54.1) 11 (55.0) 9 (52.9) 2 (50.0) 15 (60.0) 3 (37.5) Carboplatin bevacizumab 1 (2.7) 1 (5.0) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0.0) Bevacizumab 21 (95.5) 12 (100.0) 9 (90.0) 3 (100.0) 15 (93.8) 3 (100.0) Number of cycles 21.5 (1-22) 22 (8-22) 20 (1-22) 8.5 (8-9) 22 (1-22) 22 (20-22) Chemotherapy experimental protocol 1 (2.7) 1 (5.0) 0 (0.0) 0 (0.0) 1 (4.0) 0 (0.0) Total number of cycles 6 (5-8) 6 (6-8) 6 (5-6) 6 (6-8) 6 (6-8) 6 (5-6) Toxicity 15 (40.5) 9 (45.0) 6 (35.3) 3 (75.0) 9 (36.0) 3 (37.5) Post-chemotherapy CA-125 7.6 (3-67.7) 7.2 (3-67.7) 9.4 (4.2-22.2) 22.5 (5-67.7) 8.9 (4.2-22.2) 5.5 (3-14.9) Parp Inhibitors No 34 (91.9) 19 (95.0) 15 (88.2) 4 (100.0) 23 (92.0) 7 (87.5) Yes 2 (5.4) 0 (0.0) 2 (11.8) 0 (0.0) 1 (4.0) 1 (12.5) Other Center 1 (2.7) 1 (5.0) 0 (0.0) 0 (0.0) 1 (4.0) 0 (0.0) Parp regimen Olaparib 2 (100.0) 0 (0) 2 (100.0) 0 (0) 1 (100.0) 1 (100.0) Patient status Alive 26 (70.3) 14 (70.0) 12 (70.6) 1 (25.0) 17 (68.0) 8 (100.0) Dead of disease 10 (27.0) 6 (30.0) 4 (23.5) 3 (75.0) 7 (28.0) 0 (0.0) Dead for other causes 1 (2.7) 0 (0.0) 1 (5.9) 0 (0.0) 1 (4.0) 0 (0.0) Presence of disease 29 (78.4) 16 (80.0) 13 (76.5) 4 (100.0) 25 (100.0) 0 (0.0) Progression 1 (3.4) 1 (6.3) 0 (0.0) 1 (25.0) 0 (0.0) 0 (0) Relapse 28 (96.6) 15 (93.8) 13 (100.0) 3 (75.0) 25 (100.0) 0 (0) Disease localization Liver 4 (10.8) 2 (10.0) 2 (11.8) 1 (25.0) 3 (12.0) 0 (0.0) Intestinal 2 (5.4) 1 (5.0) 1 (5.9) 1 (25.0) 1 (4.0) 0 (0.0) Lymphonodal 14 (37.8) 6 (30.0) 8 (47.1) 1 (25.0) 13 (52.0) 0 (0.0) Peritoneal 10 (27.0) 6 (30.0) 4 (23.5) 2 (50.0) 8 (32.0) 0 (0.0) Pulmonary 3 (8.1) 1 (5.0) 2 (11.8) 1 (25.0) 2 (8.0) 0 (0.0) Other 11 (29.7) 8 (40.0) 3 (17.6) 3 (75.0) 8 (32.0) 0 (0.0) Median follow up (95% CI), months 44.2 (36.4-49) 42.3 (32.7-47.2) 45.6 (36.7-55.4) not reached 47.2 (42.3-55.4) 32.7 (29.3-37.7) Disease-free survival (95% CI), months 27.7 (22.7-31.9) 26.7 (12.3-31.5) 28.2 (18.5-38.0) 9.8 (9.1-infinite) 26.7 (21.0-29.7) not evaluable Overall survival (95% CI), months 62.3 (45.2-infinite) not reached 62.3 (49.6-infinite) 14.5 (13.2-infinite) 62.3 (49.6-infinite) not evaluable Results are presented as n (%) or median (min-max) as appropriate. BRCA: BReast CAncer gene. ASA: American Society of Anaesthesiologist. PFI: Platinum Free Interval. CI: Confidence Interval. § Calculated with the inverse Kaplan-Meier technique. ǂ Calculated with Kaplan-Meier method. Table 2 B Surgical characteristics, treatment characteristics and survival data of MOC patients. Characteristics Mucinous carcinoma n=10 ASA 1 0 (0.0) 2 7 (77.8) 3 2 (22.2) Classification of surgery Surgery on early stage 9 (90.0) Advanced ovarian cancer diagnostic 1 (10.0) Type of surgery Laparotomy 2 (20.0) Laparoscopy 3 (30.0) Laparoscopy plus laparotomy 5 (50.0) Intraperitoneal chemotherapy 0 (0.0) Laparoscopic evaluation 7 (70.0) Laparoscopic score 0 (0-0) Laparotomic evaluation 8 (80.0) Laparotomic score 0 (0-0) Aletti Score 1 7 (77.8) 2 2 (22.2) 3 0 (0.0) Residual tumor Absent 8 (80.0) Esplorative LPS 2 (20.0) Operating time 180 (125-240) Chemotherapy No 6 (75.0) Yes 1 (12.5) Other site 1 (12.5) Clinical setting Adjuvant 1 (50.0) Neoadjuvant 1 (50.0) Chemotherapy regimen Carboplatin taxol bevacizumab 1 (100.0) Bevacizumab 1 (100.0) Chemotherapic experimental protocol 0 (0.0) Dose frequency Thrice-weekly 1 (100.0) Total number of cycles 6 (6-6) Time to chemiotherapy 28 (28-28) Toxicity 0 (0.0) Change of chemotherapy regimen during treatment 0 (0.0) Post-chemotherapy CA-125 5 (5-5) Parp Inhibitors No 8 (100.0) Yes 0 (0.0) Other Center 0 (0.0) Patient status Alive 10 (100.0) Presence of disease 1 (10.0) Relapse 1 (100.0) Relapse localization Abdominal 1 (10.0) Results are presented as n (%) or median (min-max) as appropriate. BRCA: BReast CAncer gene. PFI: Platinum Free Interval. ASA: American Society of Anaesthesiologist. Representative images of the immunohistochemical analysis on the five antigens (EDA, EDB, FAP, CEA, and MUC16) are shown in Figure 2 A and B . Samples derived from HGSOC, LGSC and CCC exhibited a diffuse stromal and neovascular staining of EDA. A positive EDA staining was observed in forty-six (92%) of 50 neoplasm samples. In detail, F8 immunoreactivity appeared weak in 7 (14%), moderate in 22 (44%) and strong in 17 (34%) cases ( Additional Table 2 – I ). All platinum resistant patients (group C) exhibited a 2+/3+ intensity as well as 75% of BRCA WT patients (group A) ( Table 3 – I ). The L19 antibody (anti-EDB) exhibited mainly diffuse stromal and vascular smooth muscle cell staining, similar to the EDA pattern described above, while tumor cells mostly showed a negative staining. Forty out of the 50 samples (80%) expressed EDB ( Additional Table 2 – II ). In particular, eighteen (36%) of the samples exhibited a homogeneous and moderate intensity reactivity (2+ intensity), while twenty-two samples (44%) showed cells with a weak L19 intensity (1+ intensity). Additionally, ten out of 50 neoplasm samples (20%) were completely non-reactive. FAP expression was observed in 20 out of 25 cases (80%). The observed positivity was not only related to CAFs but also to the tumor stroma. Seven (28%) and 7 (28%) tissues samples showed a weak or moderate FAP expression of the stroma, respectively ( Additional Table 2-III ). There were no significant differences in L19 and FAP intensity or expression pattern when comparing the clinical subgroups ( Table 3 – II and III ). MUC16 was detected in 98% of the samples ( Additional Table 2 – IV ). There were no significant differences observed when comparing group A to group B, as well as group C to D to E ( Table 3 – IV ). In terms of intensity, 3+ was assigned to 75% of the samples in group A, 82.4% of group B, 100% of group C, 80% of group D, and 62.5% of group E. Notably, MUC16 expression was elevated in patients who experienced relapse (77.5 vs. 80.6 vs. 41.2; p=0.009). Figure 2 A shows five representative images of positive stainings obtained with the F8, L19, F4 (all Philogen), anti-FAP (Abcam) and CA 125 Clone M11 (Dako Omnis) antibodies obtained from HGSOC, CCC and LGSC tissue samples. The evaluation of CEA expression in HGSOC, CCC and LGSC tissues revealed to be mostly negative or nonspecific staining. In some of the tested specimens, the staining appeared diffuse and non-specific ( Table 3-V ). By contrast, of the 10 tested MOC samples, CEA was distributed around the cell surface with an apical/basolateral localization (indicated by arrows). The staining was evaluated as 3+ in eight out of ten samples (80%). Specifically, five samples showed an apical staining, three showed an apical and basolateral staining, and one showed both apical and luminal staining. One sample was considered negative ( Additional Table 2 – V ). No differences were observed in terms of either intensity or expression when comparing the clinical subgroups. Regarding longitudinal assessment (group F), no significant changes were observed in the expression pattern in any of the tested antigens from baseline to recurrence ( Additional Table 3 I-V ). The intensity of MUC16 shifted from 3+ to negative in one case. The intensity of F8 was diminished in one case, transitioning from 2+ to negative, whereas in five cases, it increased from 2+ to 3+ at the time of recurrence. Table 3 (I-V) summarizes the staining performances obtained across the clinical sub settings. Additional Table 2 (I-V) gives an overview of the staining performances across all cases. Table 3 (I-V) F8-Ph, L19-Ph, FAP-Abcam, MUC16-Dako and CEA-Ph Immunoreactivity across the clinical groups of HGSOC, CCC and LGSC . I. F8-Ph Intensity Neg 1+ 2+ 3+ P value* Group A: BRCA Wild type Group B: BRCA Mutated 1 (5.3) 1 (5.9) 3 (15.0) 2 (11.8) 9 (45.0) 11 (64.7) 6 (30.0) 3 (17.6) 0.80 Group C: PFI<6 months Group D: PFI≥6 months Group E: No recurrence 0 2 (8.3) 0 0 4 (16.0) 1 (12.5) 2 (50.0) 14 (56.0) 4 (50.0) 2 (50.0) 4 (16.0) 3 (37.5) 0.72 Data are given as number (percentage). F8-Ph positivity, Neg, 1+, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions). * Negative versus Positive II. L19-Ph Intensity Neg 1+ 2+ P value Group A: BRCA Wild type Group B: BRCA Mutated 4 (20.0) 3 (17.6) 9 (45.0) 8 (47.1) 7 (35.0) 6 (35.3) 0.98 Group C: PFI<6 months Group D: PFI≥6 months Group E: No recurrence 1 (25.0) 5 (20.0) 1 (12.5) 2 (50.0) 11 (44.0) 4 (50.0) 1 (25.0) 9 (36.0) 3 (37.5) 0.98 Data are given as number (percentage). L19-Ph positivity, Neg, 1+ or 2+ intensity (see MATERIALS AND METHODS for definitions). * Negative versus Positive III. FAP-Abcam Intensity Neg 1+ 2+ 3+ P value* Group A: BRCA Wild type Group B: BRCA Mutated 3 (25.0) 2 (25.0) 6 (50.0) 1 (12.5) 2 (16.7) 2 (25.0) 1 (8.3) 3 (37.5) 0.99 Group C: PFI<6 months Group D: PFI≥6 months Group E: No recurrence 1 (50.0) 4 (23.5) 0 0 7 (41.2) 0 1 (50.0) 2 (11.8) 1 (100) 0 4 (23.5) 0 ne Data are given as number (percentage). FAP-Abcam positivity, Neg, 1+, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions). * Negative versus Positive IV. MUC16-Dako Intensity 2+ 3+ P value Group A: BRCA Wild type Group B: BRCA Mutated 5 (25.0) 3 (17.6) 15 (75.0) 14 (82.4) 0.59 Group C: PFI<6 months Group D: PFI≥6 months Group E: No recurrence 0 5 (20.0) 3 (37.5) 4 (100.0) 20 (80.0) 5 (62.5) 0.31 Data are given as number (percentage). MUC16-Dako positivity, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions). * Neg versus Pos V. CEA-Ph Intensity Neg 1+ 2+ 3+ P value* Group A: BRCA Wild type Group B: BRCA Mutated 18 (90.0) 11 (64.7) 1 (5.0) 2 (11.8) 0 3 (17.6) 1 (5.0) 1 (5.9) 0.062 Group C: PFI<6 months Group D: PFI≥6 months Group E: No recurrence 3 (75.0) 20 (80.0) 6 (75.0) 0 2 (8.0) 1 (12.5) 1 (25.0) 1 (4.0) 1 (12.5) 0 2 (8.0) 0 0.94 Data are given as number (percentage). CEA-Ph positivity, Neg, 1+, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions). * Neg versus Pos Discussion EOC remains the deadliest gynaecologic cancer. Despite the advances in cytoreductive efforts, frontline chemotherapy and maintenance treatments, more than 70% of advanced OC patients relapse within two years from diagnosis. At recurrence, available treatments are limited and exhibit poor efficacy. This work provides a comparative immunohistochemical analysis of five tumor markers on samples from clinically relevant subgroups of EOC patients. Our findings showed that MUC16 and EDA exhibited a 74% and 34% rate of 3+ staining, respectively. Moreover, EDB showed a 36% rate of 2+ staining in all analyzed samples. MUC16 was found highly expressed in the vast majority of cases, especially in clinical subgroups with the greatest unmet medical need, namely platinum-resistant (100%), platinum-sensitive (80%) and BRCA WT (75%) patients. This result is in line with what has been reported by other groups (15); (19). By contrast, the expression level of MUC16 in normal tissues is low. Due to its diverse expression patterns, researchers have developed various MUC16-directed immunotherapies, including Chimeric Antigen Receptor (CAR) T-cells and bispecific antibodies, (20). Our findings not only confirm the crucial role of MUC16 in cancer progression but also highlight its potential as an excellent immunotherapeutic for addressing the most challenging scenarios in EOC. EDA was highly expressed in 50% of platinum-resistant and in 45% of BRCA WT patients. It is strongly expressed in many solid human tumors. Interestingly, it is nearly undetectable in normal tissues, offering an appealing target for antibody-cytokine fusion proteins or other therapeutic modalities targeting EDA. Regarding CEA, our results indicate that in cancer tissue sections where cells from MUC have lost their polarity, it is distributed around the cell surface, showing an apical/basolateral localization. This distinct pattern of CEA localization makes it a promising antigen for immunotherapeutic drugs in patients with Mucinous ovarian cancer. Ultimately, the consistency of staining over time was demonstrated (group F), suggesting that baseline assessments can reliably guide decisions on subsequent therapies. Major limitations of the study include the small sample size, the time frame which included a pre-PARP inhibition period and the lack of HRd assessment. Overall, these results may guide the development of novel therapeutics aiming at the antibody-based delivery of bioactive payloads such as radionuclides, drugs and cytokines to the site of disease in patients with EOC (21); (8);(22). In this context, Mirvetuximab soravtansine (MIRV) represents the first Antibody Drug Conjugate approved by the FDA (in November 2022) for the treatment of OC. MIRV consists of a humanized monoclonal antibody targeting folate receptor alpha (FR-α), linked to the cytotoxic compound DM4 through a cleavable disulfide bond. In the SORAYA study (NCT04296890) a 32.4% overall response rate was showed in pre-treated patients with platinum-resistant epithelial OC (23). Patients were included in the trial only if the tumor expressed elevated levels of FR-α, which occurred in only 36% of the patients screened. Conclusions In summary, our study endorses the exploration of MUC16- and EDA-targeting therapeutics for the treatment of HGSOC and CEA-targeting agents for MOC. Abbreviations Epithelial ovarian carcinoma (EOC), vascular endothelial growth factor (VEGF), Poly (ADP-ribose) polymerase (PARP) inhibitors, high-grade serous OC (HGSOC), CCC (clear-cell carcinoma) and low-grade serous ovarian cancer (LGOC), homologous recombination deficiency (HR-d), spliced extra-domain B (EDB), spliced extra-domain A (EDA), Fibroblast Activation Protein (FAP), cancer-associated fibroblasts (CAFs) , Carcinoembryonic antigen (CEA) , metastatic colorectal cancer (mCRC), Mucinous ovarian cancer (MOC), formalin-fixed, paraffin-embedded (FFPE), immunohistochemistry (IHC), disease-free survival (DFS), overall survival (OS), Haematoxylin and eosin (H&E), wild-type (WT), platinum-free interval (PFI), primary debulking surgery (PDS), Chimeric Antigen Receptor (CAR) T-cells, Mirvetuximab soravtansine (MIRV). Declarations Ethics approval and consent to participate Patients written informed consent was obtained before the samples collection. This is a no-profit, observational, retrospective study, approved by the Institutional Ethics Committee of ‘Fondazione Policlinico Universitario Agostino Gemelli-IRCCS’ of Rome, Italy (ID 6144). Consent for publication Not applicable. Availability of data and materials The data and matherials that support the findings of this study are available from the corresponding author upon reasonable request. Competing Interests D.N. is a co-founder and shareholder of Philogen (www.philogen.com), a Swiss-Italian Biotech company that operates in the field of ligand-based pharmacodelivery. R.D.L., F.P., L.P., and E.P., are employed by Philochem AG, a daughter company of Philogen acting as the discovery unit of the group. G.S. has been Consultant for Astrazeneca–MSD, Covidien AG, a Medtronic company, TESARO Bio Italy S.r.l. Johnson & Johnson; he also received as a speaker Bureau/Honoraria from Olympus Europa SE & CO. KG, Baxter Healthcare SA, Intuitive Surgical Inc., GlaxoSmithKline S.p.A, and honoraria/expenses from Clovis Oncology Italy S.r.l. A.F. has been Consultant for Johnson & Johnson SpA, Fondazione Internazionale Menarini, Oncoinvent AS, she also received as a speaker for: GlaxoSmithKline and Covidien/Medtronic, Grant/Researcher Support for AstraZeneca&MSD. She declares relashionship with commercial interest with AstraZeneca/MSD, Johnson & Johnson Fondazione Internazionale Menarini, GlaxoSmithKline, Oncoinvent AS, Covidien/Medtronic. C.N. received travel support from MSD, Illumina and honoraria as a speaker/advisory board from Veeva, GSK, MSD, AZ, Altems, Illumina. GFZ received as a speaker honoraria GlaxoSmithKline S.p.A. The remaining authors declare no competing interests. Funding This work was partially supported by Philogen S.p.a. Authors' contributions A.P., R.D.L., E.P., T.P., C.N., “Writing - Original Draft”; A.P., R.D.L., C.N., “Methodology”; A.P., N.D.A, A.T., T.P., D.G., “Software”, “Formal Analysis”and “Data Curation”; M.B., F.S., "Project administration” A.P., R.D.L., E.P., C.N., “Investigations” F.P., L.P., G.F.Z., A.F., D.N., G.S., “supervision” and “writing–review and editing” All authors discussed and contributed to the final manuscript, approving the submitted version. Acknowledgements We express our gratitude to Dr. Mariagrazia Valentini and Dr. Roberta Benvenuto for technical support. References Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240–53. González-Martín A, Harter P, Leary A, Lorusso D, Miller RE, Pothuri B, et al. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(10):833–48. Jiang C, Huang YH, Lu JB, Yang YZ, Rao HL, Zhang B, et al. 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ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Annals of Oncology. 2019;30(5):672–705. Hooper AT, Marquette K, Chang CPB, Golas J, Jain S, Lam MH, et al. Anti-Extra Domain B Splice Variant of Fibronectin Antibody–Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade. Mol Cancer Ther. 2022;21(9):1462–72. Schliemann C, Wiedmer A, Pedretti M, Szczepanowski M, Klapper W, Neri D. Three clinical-stage tumor targeting antibodies reveal differential expression of oncofetal fibronectin and tenascin-C isoforms in human lymphoma. Leuk Res. 2009;33(12):1718–22. Pedretti M, Soltermann A, Arni S, Weder W, Neri D, Hillinger S. Comparative immunohistochemistry of L19 and F16 in non-small cell lung cancer and mesothelioma: Two human antibodies investigated in clinical trials in patients with cancer. Lung Cancer. 2009;64(1):28–33. 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BMC Cancer. 2019;19(1):171. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42(2):377–81. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17(4):343–6. Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc. 1958;53(282):457–81. Zhai Y, Lu Q, Lou T, Cao G, Wang S, Zhang Z. MUC16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells. Ann Transl Med. 2020;8(22):1494–1494. Crawford A, Haber L, Kelly MP, Vazzana K, Canova L, Ram P, et al. A Mucin 16 bispecific T cell–engaging antibody for the treatment of ovarian cancer. Sci Transl Med. 2019;11:497. Erba PA, Sollini M, Orciuolo E, Traino C, Petrini M, Paganelli G, et al. Radioimmunotherapy with Radretumab in Patients with Relapsed Hematologic Malignancies. J Nucl Med. 2012;53(6):922–7. Neri D. Antibody–Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity. Cancer Immunol Res. 2019;7(3):348–54. Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, et al. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023;41(13):2436–45. Supplementary Files AdditionalTable1.docx AdditionalTable2.docx AdditionalTable3.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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19:03:45","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":25961,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4490240/v1/710edce464e764ab4f6b7728.docx"},{"id":59137970,"identity":"dae08885-dab8-4219-9b25-5a9d1c452b7a","added_by":"auto","created_at":"2024-06-26 19:03:45","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":25259,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalTable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4490240/v1/321da0c2152524db38bc389d.docx"},{"id":59137968,"identity":"5fba3d51-687c-4a4e-a9b1-34d8d8b23ed3","added_by":"auto","created_at":"2024-06-26 19:03:44","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":27082,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalTable3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4490240/v1/31b29434e409a90bffde1c19.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eIdentifying New Therapeutic Targets in Epithelial Ovarian Cancer\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eEpithelial ovarian carcinoma (EOC) is the leading cause of death among all gynecological cancers in developed countries, mainly due to the lack of early diagnosis coupled with the frequent acquisition of resistance to available treatments (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In the past decade, the therapeutic landscape for EOC has witnessed a significant evolution. Initially centered around debulking surgery and platinum-based chemotherapy, the treatment algorithm has since been enriched by the integration of targeted therapies such as vascular endothelial growth factor (VEGF) and Poly (ADP-ribose) polymerase (PARP) inhibitors (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe optimal positioning of current available therapies within the EOC treatment algorithm remains challenging. Indirect and not exhaustive biomarkers for platinum-based chemotherapy and PARP inhibitors sensitivity in high-grade serous OC (HGSOC) patients, are BRCA1/2 genes mutations and homologous recombination deficiency (HR-d). Patients harboring these genomic alterations have a defective DNA double-strand break repair mechanism, making chemotherapy cytotoxic anti-cancer activity more effective. Yet, chemotherapy does not discriminate healthy from malignant proliferating cells, leading to a high toxicity profile. No predictive biomarkers of response to the VEGF inhibitor Bevacizumab are currently available and the overall survival benefit that this drug promotes remains questionable in many cancers(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003eFurthermore, the emergence of \u003cem\u003ede novo\u003c/em\u003e or acquired resistance to these novel therapies is emerging as relevant unmet need in recurrent settings, with no available tumor biomarkers for such challenges. These biomarkers could be exploited for the selective delivery of bioactive payloads to the site of disease. Approximately 20% of EOC patients that currently do not respond to any standard therapy, may benefit from the development of such innovative treatment approaches (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e); (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e); (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe alternatively spliced extra-domain B (EDB) and A (EDA) of fibronectin are among the best-characterized markers of angiogenesis. Both domains are virtually undetectable in normal adult tissues (with the exception of the endometrium in the proliferative phase and some vessels of the ovaries) but are strongly expressed in most aggressive cancers, with a prominent vascular and stromal pattern of expression (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e); (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e): (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The fully human monoclonal antibodies L19 and F8 have been isolated encoded combinatorial libraries and are directed against the alternatively-spliced EDB and EDA domains of fibronectin, respectively (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). These antibodies have been shown to selectively localize around tumor neo-vasculature structures in animal cancer models and in patients, making them valuable tools for cancer research and potential therapeutic applications.\u003c/p\u003e \u003cp\u003eFibroblast Activation Protein (FAP) is a transmembrane serine protease rarely expressed in healthy adult tissues but abundantly expressed on the surface of cancer-associated fibroblasts (CAFs) and in the stroma of pathological conditions such as cancer. The antigen has garnered significant attention as the 'next billion-dollar nuclear theranostics target', based on the successful imaging data generated in over 28 different tumor types in patients using radiolabeled FAP-targeting ligands (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCarcinoembryonic antigen (CEA) is a well-validated cell surface antigen primarily associated with metastatic colorectal cancer (mCRC). Additionally, it is expressed in breast, liver, lung, stomach, pancreatic, ovarian cancers and other malignancies. Structurally, CEA is a GPI-anchored membrane protein comprising seven Ig-like domains. In healthy organs, CEA expression remains confined to the apical surface of mature enterocytes, rendering it virtually inaccessible to circulating antibodies. However, in malignant cells, the polarity of CEA expression is disrupted, leading to its exposure to the vasculature and lymphatic system. The immunohistochemical staining of CEA plays an essential role in differential diagnosis of Mucinous ovarian cancer (MOC) from other possible subtypes of EOC. The fully human monoclonal antibody F4 has been isolated from a phage display library and has been shown to selectively localize in CEA-positive tumors in preclinical models ((\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMUC16, commonly known as CA-125, represents a promising and valuable antigen for targeted immunotherapy for the treatment of OC. This antigen has emerged as a focal point of interest in cancer research due to its crucial role in disease pathogenesis and progression. MUC16 overexpression has been extensively linked to various detrimental cellular processes. Elevated levels of the antigen have been associated with enhanced cell proliferation, facilitating the uncontrolled growth of cancer cells. Furthermore, it has been implicated in promoting the migration and invasion of tumor cells, leading to the metastatic spread of the disease (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this article, we present the results of a comparative immunohistochemical evaluation of five validated antibodies F8 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), L19 (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), anti-FAP (Abcam), F4 (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)and CA 125 Clone M11 (Dako Omnis), specific to EDA, EDB, FAP, CEA, and MUC16, respectively, on selected EOC patient samples. The tested antibodies represent suitable delivery vehicles for various anti-cancer payloads (e.g., cytokines or cytotoxics) for the treatment of EOC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients and study design\u003c/h2\u003e \u003cp\u003e This is a no-profit, observational, retrospective study, approved by the Institutional Ethics Committee (ID 6144).\u003c/p\u003e \u003cp\u003eThe inclusion criteria were defined as follows: patients with histological diagnosis of EOC, available formalin-fixed, paraffin-embedded (FFPE) tissues at diagnosis (baseline), updated clinical information (baseline information, pathological and molecular features when applicable, medical and surgical treatments, follow-up) and available signed informed consent. Patients were excluded in case of non-epithelial histology and less than 30% of tumor cells in the FPPE specimen. For eligible patients, clinical data were retrieved from their medical records.\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAn immunohistochemistry (IHC) analysis with a panel of antibodies for the immuno-oncology targets EDA, EDB, FAP, CEA and MUC16 was performed on one representative tissue sample from a tumor block of all cases at baseline and, when available, at relapse.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003ePseudo-anonymized data were collected and managed using REDCap electronic data capture tools hosted at \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://redcap-irccs.policlinicogemelli.it/\u003c/span\u003e\u003cspan address=\"https://redcap-irccs.policlinicogemelli.it/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). All data were processed in compliance with European Regulation on the Privacy of data (UE 2016/679).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eA total number of 60 samples was estimated based on the intensity and expression of the above reported antibodies on EOC samples according to Human Protein Atlas (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.proteinatlas.org/\u003c/span\u003e\u003cspan address=\"https://www.proteinatlas.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e; L19 antibody 58%, F8 antibody: 92%, anti-FAP antibody: 30%, anti-CEA antibody: 10% and anti-MUC16 antibody: 100%).\u003c/p\u003e \u003cp\u003eContinuous variables were summarized as medians and interquartile ranges and differences between variables were analyzed by using the Mann-Whitney U test. Categorical variables were used to express the number of cases and percentages (%). Associations have been assessed by the chi-square or Fisher exact test, used as appropriate according to the expected frequency in each cell and differences in mean values were examined through the Student\u0026rsquo;s t-test.\u003c/p\u003e \u003cp\u003eMedian follow up was calculated with the inverse Kaplan-Meier technique (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Survival outcomes were presented in terms of both disease-free survival (DFS) and overall survival (OS). DFS was defined as the time that elapsed from the first pathological diagnosis to recurrence or last follow-up, whereas OS was defined as the time from the first pathological diagnosis to death or last follow-up. Median OS and DFS were estimated with the Kaplan\u0026ndash;Meier product limit method (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) and were presented with a 95% confidence interval. All statistical tests used a two-tailed α of 0.05. All analyses were performed using SPSS version 24.0.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eSample processing\u003c/h2\u003e \u003cp\u003eThe FFPE tissue blocks were collected and cut into 3-\u0026micro;m thick sections. Haematoxylin and eosin (H\u0026amp;E) stained sections from FFPE were double-blind reviewed by two expert pathologists. IHC staining of FFPE tissues was performed with the F8, L19 and F4 antibodies (Philogen), anti-FAP (Abcam) and CA 125 Clone M11 (Dako Omnis), followed by appropriate secondary monoclonal rabbit anti-human antibodies using the BOND Polymer Refine Detection on the Bond III automated immunostainer (Leica Microsystems, Bannockburn, IL). A negative and positive control staining versus reactivity with the mAbs was performed in each series.\u003c/p\u003e \u003cp\u003eThe F8, L19, anti-FAP and anti-MUC16 staining was evaluated based on the intensity signal (absent, 0; weak, 1+; moderate, 2+; strong, 3+) and the percentage of positive immunoreactive cells for the respective target (EDA, EDB, FAP, and MUC16, respectively). The results of CEA immunohistochemical staining were interpreted based on the localization pattern of the antigen in MOC tissues: (0; negative/absent staining), (1; staining restricted to the apical membrane: apical-type), (2; staining on the apical/basolateral cellular membrane), (3; staining on the apical and luminal). The antibody clones did not have the same affinity towards their cognate antigen, so they were used at different concentrations.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBetween March 2016 and March 2024, a total of 47 patients with EOC were retrospectively enrolled. Baseline samples were accessible for all patients, with 13 of them additionally having matched biopsy samples taken at the time of relapse. Patients with HGSOC, CCC\u0026nbsp;(clear-cell carcinoma) and low-grade serous ovarian cancer (LGOC) were further categorized based on clinico-molecular characteristics:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eGroup A: Patients with wild-type (WT) BRCA1/2 genes (n=20)\u003c/li\u003e\n \u003cli\u003eGroup B: Patients with mutant BRCA1/2 genes (n=17)\u003c/li\u003e\n \u003cli\u003eGroup C: Patients who experienced recurrence with a platinum-free interval (PFI) of less than 6 months (n=4)\u003c/li\u003e\n \u003cli\u003eGroup D: Patients who experienced recurrence with a platinum-free interval (PFI) of more than 6 months (n=25)\u003c/li\u003e\n \u003cli\u003eGroup E: Patients who did not experience relapse (n=8)\u003c/li\u003e\n \u003cli\u003eGroup F: Patients with matched baseline and recurrence samples (n=13)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eMOC patients were considered separately, and tested only for CEA (group G, n=10) (\u003cstrong\u003eFigure 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eClinico-pathological characteristics of enrolled patients are summarized in \u003cstrong\u003eTable 1 A and B\u003c/strong\u003e; \u003cstrong\u003eAdditional Table 1\u003c/strong\u003e shows the ones of matched sample at recurrence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn detail, the IHC analysis\u0026nbsp;using the\u0026nbsp;F8, L19, anti-FAP, CEA and anti-MUC16 antibodies was performed on 37 ovary primary tumors, 12 peritoneal and one vaginal nodule metastasis. In addition, on the MOC samples, the anti-CEA staining was performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1A\u003c/strong\u003e. Clinical HGSOC, CCC, LGSC patients\u0026rsquo; characteristics\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"641\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.232449297971918%\" rowspan=\"2\"\u003e\n \u003cp\u003eCharacteristic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.636505460218409%\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAll cases\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=37\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.429017160686428%\" colspan=\"2\"\u003e\n \u003cp\u003eBRCA status\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.636505460218409%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"38.06552262090484%\" colspan=\"3\"\u003e\n \u003cp\u003eDisease status\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup A: Wild type\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup B: Mutated\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup C: PFI \u0026lt; 6 months\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup D: PFI \u0026ge; 6 months\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=25\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup E:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eAbsence of recurrence\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eAge at diagnosis, years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e52 (33-73)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e55.5 (33-73)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e51 (39-64)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e54 (47-57)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e49 (37-73)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e58.5 (33-62)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e24.1 (18.2-34.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e24.1 (18.2-32)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e24.1 (18.5-34.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e23.6 (19.2-30.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e24.8 (18.2-34.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e23.1 (18.5-34.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eBody mass index classification\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eUnderweight\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (10.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (8.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eNormal weight\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e19 (51.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (50.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (52.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e11 (44.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (62.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eOverweight\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e11 (29.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (30.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (29.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (40.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eObese\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (13.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (10.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (17.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (8.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003ePost menopause\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e18 (50.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (52.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (47.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (40.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (71.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eSymptoms at diagnosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo symptoms\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (16.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (10.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (23.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (12.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbdominal pain\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e14 (37.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (50.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (23.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (50.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (40.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbdominal distension\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (21.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (17.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (28.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eBlood loss\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (8.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (11.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eOther\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (16.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (10.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (23.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (16.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eCA-125 at diagnosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e418.5 (5-17730)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e768.5 (5-17730)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e301.9 (55.7-2272)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e6652 (95.8-17730)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e462.5 (5-5814.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e177.3 (55.7-13110)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eECOG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e27 (73.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e13 (65.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e14 (82.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e18 (72.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (27.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (35.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (17.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (28.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eHistotype\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eSerous high-grade carcinoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e35 (94.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e19 (95.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e16 (94.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e24 (96.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (87.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eSerous low-grade carcinoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eClear cells carcinoma\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrading\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e35 (94.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e19 (95.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e16 (94.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e24 (96.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (87.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eFIGO stage\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eIIIA1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (10.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eIIIA2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eIIIB\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eIIIC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (59.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e11 (55.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e11 (64.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e17 (68.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (50.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eIVA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.267605633802816%\" valign=\"bottom\"\u003e\n \u003cp\u003eIVB\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (21.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (17.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (20.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.67605633802817%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eClinical HGSOC, CCC, LGSC patients\u0026rsquo; characteristics\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1 B\u0026nbsp;\u003c/strong\u003eClinical MOC patients\u0026rsquo; characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\"\u003e\n \u003cp\u003eGroup G= Mucinous carcinoma\u003cbr\u003e\u0026nbsp;n=10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eAge at diagnosis, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e46.5 (34-75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eBody mass index, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e22.9 (20.5-37.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eBody mass index classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eUnderweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eNormal weight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eOverweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eObese\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003ePost menopause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eSymptoms at diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbdominal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbdominal distension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eBlood loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eCA-125 at diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e65.7 (12.6-383)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eHistotype\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eMucinous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrading\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eFIGO stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eIC1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eIC2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"60.60606060606061%\" valign=\"bottom\"\u003e\n \u003cp\u003eIIIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"39.39393939393939%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eResults are presented as n (%) or median (min-max) as appropriate. BRCA: BReast CAncer gene. PFI: Platinum Free Interval. ECOG: Eastern Cooperative Oncology Group. FIGO: international federation of gynaecology and obstetrics.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNo relevant difference in baseline clinical characteristics was found across the groups. The vast majority of patients was diagnosed with HGSOC. No relevant differences in terms of age were observed between the groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData on surgery, treatment, and survival characteristics are reported in \u003cstrong\u003eTable 2 A and B\u003c/strong\u003e. All patients underwent primary debulking surgery (PDS) and an absent residual tumor was achieved in 94.4% of cases. All patients received platinum-based chemotherapy as first-line treatment, achieving a favorable biochemical response demonstrated by a decrease in CA-125 levels to within normal range. The significant majority (95.5%) of patients received bevacizumab both during chemotherapy and as part of maintenance. In group B, two patients received PARP inhibitors in first-line. Of all enrolled patients, 75.6% experienced recurrence, with the disease primarily localized in the peritoneum or lymph nodes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 A\u0026nbsp;\u003c/strong\u003eSurgical treatment and survival characteristics data of HGSOC, CCC, LGSC patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"697\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" rowspan=\"2\"\u003e\n \u003cp\u003eCharacteristic\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" rowspan=\"2\"\u003e\n \u003cp\u003eAll cases\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=37\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\"\u003e\n \u003cp\u003eBRCA status\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.5%\" colspan=\"3\"\u003e\n \u003cp\u003eDisease status\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup A: Wild type\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=20\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup B: Mutated\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=17\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup C: PFI \u0026lt; 6 months\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup D: PFI \u0026ge; 6 months\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=25\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.666666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eGroup E: Absence of recurrence\u0026nbsp;\u003cbr\u003e\u0026nbsp;n=8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003eASA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (29.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (23.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (40.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (57.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e18 (66.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (70.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (60.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (28.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (3.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (14.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003ePrimary debulking surgery\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e37 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e20 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e17 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e25 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003eIntraperitoneal chemotherapy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (11.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (8.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003eAletti Score\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (40.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (35.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (47.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (36.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (62.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e20 (54.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (60.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (47.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (60.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003eResidual tumor\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbsent\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e34 (94.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e18 (94.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e16 (94.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (91.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026lt; = 0.5 cm\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (8.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003eOperating\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e380 (180-660)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e370 (240-660)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e385 (180-600)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e402.5 (270-660)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e390 (180-600)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e270 (240-491)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eChemotherapy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e37 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e20 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e17 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e25 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eChemotherapy regimen\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eCarboplatin taxol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eCarboplatin taxol bevacizumab\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e20 (54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e11 (55.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eCarboplatin bevacizumab\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eBevacizumab\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e21 (95.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (90.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (93.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eNumber of cycles\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e21.5 (1-22)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (8-22)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e20 (1-22)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.5 (8-9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (1-22)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (20-22)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eChemotherapy experimental protocol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eTotal number of cycles\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (5-8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (6-8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (5-6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (6-8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (6-8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (5-6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eToxicity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (40.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (45.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (35.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (36.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (37.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003ePost-chemotherapy CA-125\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.6 (3-67.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.2 (3-67.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.4 (4.2-22.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e22.5 (5-67.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.9 (4.2-22.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e5.5 (3-14.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eParp Inhibitors\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e34 (91.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e19 (95.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (88.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e23 (92.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (87.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (11.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eOther Center\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eParp regimen\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.166666666666668%\" valign=\"bottom\"\u003e\n \u003cp\u003eOlaparib\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.5%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.625%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003ePatient status\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eAlive\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e26 (70.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e14 (70.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (70.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e17 (68.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eDead of disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (27.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (30.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (23.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (28.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eDead for other causes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003ePresence of disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e29 (78.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e16 (80.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e13 (76.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e25 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eProgression\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (3.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (6.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eRelapse\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e28 (96.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e15 (93.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e13 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e25 (100.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eDisease localization\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eLiver\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (10.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (10.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (11.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (12.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eIntestinal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eLymphonodal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e14 (37.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (30.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (47.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e13 (52.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003ePeritoneal\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (27.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (30.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (23.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (50.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (32.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003ePulmonary\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (8.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (5.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (11.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (25.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (8.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eOther\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e11 (29.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (40.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (17.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (75.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (32.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian follow up (95% CI), months\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e44.2 (36.4-49)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\"\u003e\n \u003cp\u003e42.3 (32.7-47.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e45.6 (36.7-55.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003enot reached\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\"\u003e\n \u003cp\u003e47.2 (42.3-55.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\"\u003e\n \u003cp\u003e32.7 (29.3-37.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eDisease-free survival (95% CI), months\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e27.7 (22.7-31.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003e26.7 (12.3-31.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e28.2 (18.5-38.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.8 (9.1-infinite)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e26.7 (21.0-29.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003enot evaluable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.125%\" valign=\"bottom\"\u003e\n \u003cp\u003eOverall survival (95% CI), months\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e62.3 (45.2-infinite)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.416666666666666%\" valign=\"bottom\"\u003e\n \u003cp\u003enot reached\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e62.3 (49.6-infinite)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"1.0416666666666667%\" valign=\"bottom\"\u003e\n \u003cp\u003e \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e14.5 (13.2-infinite)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.458333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003e62.3 (49.6-infinite)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.583333333333334%\" valign=\"bottom\"\u003e\n \u003cp\u003enot evaluable\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"8\" valign=\"top\"\u003e\n \u003cp\u003eResults are presented as n (%) or median (min-max) as appropriate. BRCA: BReast CAncer gene. ASA: American Society of Anaesthesiologist. \u0026nbsp;PFI: Platinum Free Interval. CI: Confidence Interval. \u0026sect; Calculated with the inverse Kaplan-Meier technique. ǂ Calculated with Kaplan-Meier method.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"697\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable 2 B\u003c/strong\u003e Surgical characteristics, treatment characteristics and survival data of MOC patients.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\"\u003e\n \u003cp\u003eMucinous carcinoma\u003cbr\u003e\u0026nbsp;n=10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (77.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eClassification of surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eSurgery on early stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (90.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eAdvanced ovarian cancer diagnostic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eType of surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparoscopy plus laparotomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eIntraperitoneal chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparoscopic evaluation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (70.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparoscopic score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparotomic evaluation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eLaparotomic score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eAletti Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (77.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eResidual tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eEsplorative LPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eOperating time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e180 (125-240)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eOther site\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eClinical setting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eAdjuvant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eNeoadjuvant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eChemotherapy regimen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eCarboplatin taxol bevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eBevacizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eChemotherapic experimental protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eDose frequency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eThrice-weekly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eTotal number of cycles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 (6-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eTime to chemiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e28 (28-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eChange of chemotherapy regimen during treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003ePost-chemotherapy CA-125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (5-5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eParp Inhibitors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eOther Center\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003ePatient status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eAlive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003ePresence of disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eRelapse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eRelapse localization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.48206599713056%\" valign=\"bottom\"\u003e\n \u003cp\u003eAbdominal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"87.51793400286944%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eResults are presented as n (%) or median (min-max) as appropriate. BRCA: BReast CAncer gene. PFI: Platinum Free Interval. ASA: American Society of Anaesthesiologist.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eRepresentative images of the immunohistochemical analysis on the five antigens (EDA, EDB, FAP, CEA, and MUC16) are shown in \u003cstrong\u003eFigure 2 A and B\u003c/strong\u003e. Samples derived from HGSOC, LGSC and CCC exhibited a diffuse stromal and neovascular staining of EDA. A positive EDA staining was observed in forty-six (92%) of 50 neoplasm samples. In detail, F8 immunoreactivity appeared weak in 7 (14%), moderate in 22 (44%) and strong in 17 (34%) cases (\u003cstrong\u003eAdditional Table 2 \u0026ndash; I\u003c/strong\u003e). All platinum resistant patients (group C) exhibited a 2+/3+ intensity as well as 75% of BRCA WT patients (group A) (\u003cstrong\u003eTable 3 \u0026ndash; I\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eThe L19 antibody (anti-EDB) exhibited mainly diffuse stromal and vascular smooth muscle cell staining, similar to the EDA pattern described above, while tumor cells mostly showed a negative staining. Forty out of the 50 samples (80%) expressed EDB (\u003cstrong\u003eAdditional Table 2 \u0026ndash; II\u003c/strong\u003e). In particular, eighteen (36%) of the samples exhibited a homogeneous and moderate intensity reactivity (2+ intensity), while twenty-two samples (44%) showed cells with a weak L19 intensity (1+ intensity). Additionally, ten out of 50 neoplasm samples (20%) were completely non-reactive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFAP expression was observed in 20 out of 25 cases (80%). The observed positivity was not only related to CAFs but also to the tumor stroma. Seven (28%) and 7 (28%) tissues samples showed a weak or moderate FAP expression of the stroma, respectively\u0026nbsp;(\u003cstrong\u003eAdditional Table 2-III\u003c/strong\u003e). There were no significant differences in L19 and FAP\u0026nbsp;intensity or expression pattern when comparing the clinical subgroups (\u003cstrong\u003eTable 3 \u0026ndash; II and III\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eMUC16 was detected in 98% of the samples (\u003cstrong\u003eAdditional Table 2 \u0026ndash; IV\u003c/strong\u003e). There were no significant differences observed when comparing group A to group B, as well as group C to D to E (\u003cstrong\u003eTable 3 \u0026ndash; IV\u003c/strong\u003e). In terms of intensity, 3+ was assigned to 75% of the samples in group A, 82.4% of group B, 100% of group C, 80% of group D, and 62.5% of group E. Notably, MUC16 expression was elevated in patients who experienced relapse (77.5 vs. 80.6 vs. 41.2; p=0.009). \u003cstrong\u003eFigure 2 A\u003c/strong\u003e shows five representative images of positive stainings obtained with the F8, L19, F4 (all Philogen), anti-FAP (Abcam) and CA 125 Clone M11 (Dako Omnis) antibodies obtained from HGSOC, CCC and LGSC tissue samples.\u003c/p\u003e\n\u003cp\u003eThe evaluation of CEA expression in HGSOC, CCC and LGSC tissues revealed to be mostly negative or nonspecific staining. In some of the tested specimens, the staining appeared diffuse and non-specific (\u003cstrong\u003eTable 3-V\u003c/strong\u003e). By contrast, of the 10 tested MOC samples, CEA was distributed around the cell surface with an apical/basolateral localization (indicated by arrows). The staining was evaluated as 3+ in eight out of ten samples (80%). Specifically, five samples showed an apical staining, three showed an apical and basolateral staining, and one showed both apical and luminal staining. One sample was considered negative (\u003cstrong\u003eAdditional Table 2 \u0026ndash; V\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eNo differences were observed in terms of either intensity or expression when comparing the clinical subgroups.\u0026nbsp;Regarding longitudinal assessment (group F), no significant changes were observed in the expression pattern in any of the tested antigens from baseline to recurrence (\u003cstrong\u003eAdditional Table 3 I-V\u003c/strong\u003e). The intensity of MUC16 shifted from 3+ to negative in one case. The intensity of F8 was diminished in one case, transitioning from 2+ to negative, whereas in five cases, it increased from 2+ to 3+ at the time of recurrence. \u003cstrong\u003eTable 3 (I-V)\u003c/strong\u003e summarizes the staining performances obtained across the clinical sub settings. \u003cstrong\u003eAdditional Table 2 (I-V)\u003c/strong\u003e gives an overview of the staining performances across all cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3 (I-V)\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eF8-Ph, L19-Ph, FAP-Abcam, MUC16-Dako and CEA-Ph Immunoreactivity\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eacross the clinical groups of HGSOC, CCC and LGSC\u003c/strong\u003e. \u0026nbsp;\u003cbr\u003e\u0026nbsp;I. F8-Ph Intensity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.09917355371901%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e3+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003eP value*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.09917355371901%\" valign=\"top\"\u003e\n \u003cp\u003eGroup A: BRCA Wild type\u003c/p\u003e\n \u003cp\u003eGroup B: BRCA Mutated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e1 (5.3)\u003c/p\u003e\n \u003cp\u003e1 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e3 (15.0)\u003c/p\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e9 (45.0)\u003c/p\u003e\n \u003cp\u003e11 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e6 (30.0)\u003c/p\u003e\n \u003cp\u003e3 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.09917355371901%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C: PFI\u0026lt;6 months\u003c/p\u003e\n \u003cp\u003eGroup D: PFI\u0026ge;6 months\u003c/p\u003e\n \u003cp\u003eGroup E: No recurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2 (8.3)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e4 (16.0)\u003c/p\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.702479338842975%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0)\u003c/p\u003e\n \u003cp\u003e14 (56.0)\u003c/p\u003e\n \u003cp\u003e4 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0)\u003c/p\u003e\n \u003cp\u003e4 (16.0)\u003c/p\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.049586776859504%\" valign=\"top\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are given as number (percentage). F8-Ph positivity, Neg, 1+, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions).\u003c/p\u003e\n\u003cp\u003e* Negative versus Positive\u003c/p\u003e\n\u003cp\u003eII. L19-Ph Intensity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.286189683860233%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.3044925124792%\" valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.806988352745424%\" valign=\"top\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.633943427620633%\" valign=\"top\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.286189683860233%\" valign=\"top\"\u003e\n \u003cp\u003eGroup A: BRCA Wild type\u003c/p\u003e\n \u003cp\u003eGroup B: BRCA Mutated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.3044925124792%\" valign=\"top\"\u003e\n \u003cp\u003e4 (20.0)\u003c/p\u003e\n \u003cp\u003e3 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.806988352745424%\" valign=\"top\"\u003e\n \u003cp\u003e9 (45.0)\u003c/p\u003e\n \u003cp\u003e8 (47.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.633943427620633%\" valign=\"top\"\u003e\n \u003cp\u003e7 (35.0)\u003c/p\u003e\n \u003cp\u003e6 (35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.286189683860233%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C: PFI\u0026lt;6 months\u003c/p\u003e\n \u003cp\u003eGroup D: PFI\u0026ge;6 months\u003c/p\u003e\n \u003cp\u003eGroup E: No recurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.3044925124792%\" valign=\"top\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003cp\u003e5 (20.0)\u003c/p\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.806988352745424%\" valign=\"top\"\u003e\n \u003cp\u003e2 (50.0)\u003c/p\u003e\n \u003cp\u003e11 (44.0)\u003c/p\u003e\n \u003cp\u003e4 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.633943427620633%\" valign=\"top\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003cp\u003e9 (36.0)\u003c/p\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.96838602329451%\" valign=\"top\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are given as number (percentage). L19-Ph positivity, Neg, 1+ or 2+ intensity (see MATERIALS AND METHODS for definitions).\u003c/p\u003e\n\u003cp\u003e* Negative versus Positive\u003c/p\u003e\n\u003cp\u003eIII. FAP-Abcam Intensity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.633165829145728%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.74036850921273%\" valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.39530988274707%\" valign=\"top\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.39530988274707%\" valign=\"top\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.557788944723619%\" valign=\"top\"\u003e\n \u003cp\u003e3+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.278056951423785%\" valign=\"top\"\u003e\n \u003cp\u003eP value*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.633165829145728%\" valign=\"top\"\u003e\n \u003cp\u003eGroup A: BRCA Wild type\u003c/p\u003e\n \u003cp\u003eGroup B: BRCA Mutated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.74036850921273%\" valign=\"top\"\u003e\n \u003cp\u003e3 (25.0)\u003c/p\u003e\n \u003cp\u003e2 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.39530988274707%\" valign=\"top\"\u003e\n \u003cp\u003e6 (50.0)\u003c/p\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.39530988274707%\" valign=\"top\"\u003e\n \u003cp\u003e2 (16.7)\u003c/p\u003e\n \u003cp\u003e2 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.557788944723619%\" valign=\"top\"\u003e\n \u003cp\u003e1 (8.3)\u003c/p\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.278056951423785%\" valign=\"top\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"26.633165829145728%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C: PFI\u0026lt;6 months\u003c/p\u003e\n \u003cp\u003eGroup D: PFI\u0026ge;6 months\u003c/p\u003e\n \u003cp\u003eGroup E: No recurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.74036850921273%\" valign=\"top\"\u003e\n \u003cp\u003e1 (50.0)\u003c/p\u003e\n \u003cp\u003e4 (23.5)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.39530988274707%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e7 (41.2)\u003c/p\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.39530988274707%\" valign=\"top\"\u003e\n \u003cp\u003e1 (50.0)\u003c/p\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003cp\u003e1 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.557788944723619%\" valign=\"top\"\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (23.5)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.278056951423785%\" valign=\"top\"\u003e\n \u003cp\u003ene\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are given as number (percentage). FAP-Abcam positivity, Neg, 1+, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions).\u003c/p\u003e\n\u003cp\u003e* Negative versus Positive\u003c/p\u003e\n\u003cp\u003eIV. MUC16-Dako Intensity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.45424292845258%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.459234608985025%\" valign=\"top\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.459234608985025%\" valign=\"top\"\u003e\n \u003cp\u003e3+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.62728785357737%\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.45424292845258%\" valign=\"top\"\u003e\n \u003cp\u003eGroup A: BRCA Wild type\u003c/p\u003e\n \u003cp\u003eGroup B: BRCA Mutated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.459234608985025%\" valign=\"top\"\u003e\n \u003cp\u003e5 (25.0)\u003c/p\u003e\n \u003cp\u003e3 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.459234608985025%\" valign=\"top\"\u003e\n \u003cp\u003e15 (75.0)\u003c/p\u003e\n \u003cp\u003e14 (82.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.62728785357737%\" valign=\"top\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.45424292845258%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C: PFI\u0026lt;6 months\u003c/p\u003e\n \u003cp\u003eGroup D: PFI\u0026ge;6 months\u003c/p\u003e\n \u003cp\u003eGroup E: No recurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.459234608985025%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e5 (20.0)\u003c/p\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.459234608985025%\" valign=\"top\"\u003e\n \u003cp\u003e4 (100.0)\u003c/p\u003e\n \u003cp\u003e20 (80.0)\u003c/p\u003e\n \u003cp\u003e5 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.62728785357737%\" valign=\"top\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are given as number (percentage). MUC16-Dako positivity, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions).\u003c/p\u003e\n\u003cp\u003e* Neg versus Pos\u003c/p\u003e\n\u003cp\u003eV. CEA-Ph Intensity\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.523489932885905%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e1+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.939597315436242%\" valign=\"top\"\u003e\n \u003cp\u003e2+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e3+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.751677852348994%\" valign=\"top\"\u003e\n \u003cp\u003eP value*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.523489932885905%\" valign=\"top\"\u003e\n \u003cp\u003eGroup A: BRCA Wild type\u003c/p\u003e\n \u003cp\u003eGroup B: BRCA Mutated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e18 (90.0)\u003c/p\u003e\n \u003cp\u003e11 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003cp\u003e2 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.939597315436242%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e3 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e1 (5.0)\u003c/p\u003e\n \u003cp\u003e1 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.751677852348994%\" valign=\"top\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.523489932885905%\" valign=\"top\"\u003e\n \u003cp\u003eGroup C: PFI\u0026lt;6 months\u003c/p\u003e\n \u003cp\u003eGroup D: PFI\u0026ge;6 months\u003c/p\u003e\n \u003cp\u003eGroup E: No recurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e3 (75.0)\u003c/p\u003e\n \u003cp\u003e20 (80.0)\u003c/p\u003e\n \u003cp\u003e6 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2 (8.0)\u003c/p\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.939597315436242%\" valign=\"top\"\u003e\n \u003cp\u003e1 (25.0)\u003c/p\u003e\n \u003cp\u003e1 (4.0)\u003c/p\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.261744966442953%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2 (8.0)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.751677852348994%\" valign=\"top\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are given as number (percentage). \u0026nbsp;CEA-Ph positivity, Neg, 1+, 2+ or 3+ intensity (see MATERIALS AND METHODS for definitions).\u003c/p\u003e\n\u003cp\u003e* Neg versus Pos\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eEOC remains the\u0026nbsp;deadliest gynaecologic cancer. Despite the advances in cytoreductive efforts, frontline chemotherapy and maintenance treatments, more than 70% of advanced OC patients relapse within two years from diagnosis. At recurrence, available treatments are limited and exhibit poor efficacy.\u003c/p\u003e\n\u003cp\u003eThis work provides a comparative immunohistochemical analysis of five tumor markers on samples from clinically relevant subgroups of EOC patients. Our findings showed that MUC16 and EDA exhibited a 74% and 34% rate of 3+ staining, respectively. Moreover, EDB showed a 36% rate of 2+ staining in all analyzed samples.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMUC16 was found highly expressed in the vast majority of cases, especially in clinical subgroups with the greatest unmet medical need, namely platinum-resistant (100%), platinum-sensitive (80%) and BRCA WT (75%) patients. This result is in line with what has been reported by other groups (15); (19). By contrast, the expression level of MUC16 in normal tissues is low. Due to its diverse expression patterns, researchers have developed various MUC16-directed immunotherapies, including Chimeric Antigen Receptor (CAR) T-cells and bispecific antibodies, (20). Our findings not only confirm the crucial role of MUC16 in cancer progression but also highlight its potential as an excellent immunotherapeutic\u0026nbsp;for addressing the most challenging scenarios in EOC.\u003c/p\u003e\n\u003cp\u003eEDA was highly expressed in 50% of platinum-resistant and in 45% of BRCA WT patients. It is strongly expressed in many solid human tumors. Interestingly, it is nearly undetectable in normal tissues, offering an appealing target for antibody-cytokine fusion proteins or other therapeutic modalities targeting EDA.\u003c/p\u003e\n\u003cp\u003eRegarding CEA, our results indicate that in cancer tissue sections where cells from MUC have lost their polarity, it is distributed around the cell surface, showing an apical/basolateral localization. This distinct pattern of CEA localization makes it a promising antigen for immunotherapeutic drugs in patients with Mucinous ovarian cancer. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUltimately, the consistency of staining over time was demonstrated (group F), suggesting that baseline assessments can reliably guide decisions on subsequent therapies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMajor limitations of the study include the small sample size, the time frame which included a pre-PARP inhibition period and the lack of HRd assessment.\u003c/p\u003e\n\u003cp\u003eOverall, these results may guide the development of novel therapeutics aiming at the antibody-based delivery of bioactive payloads such as radionuclides, drugs and cytokines to the site of disease in patients with EOC (21); (8);(22).\u003c/p\u003e\n\u003cp\u003eIn this context, Mirvetuximab soravtansine (MIRV) represents the first Antibody Drug Conjugate approved by the FDA (in November 2022) for the treatment of OC. MIRV consists of a humanized monoclonal antibody targeting folate receptor alpha (FR-\u0026alpha;), linked to the cytotoxic compound DM4 through a cleavable disulfide bond. In the SORAYA study (NCT04296890) a 32.4% overall response rate was showed in pre-treated patients with platinum-resistant epithelial OC (23). Patients were included in the trial only if the tumor expressed elevated levels of FR-\u0026alpha;, which occurred in only 36% of the patients screened.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, our study endorses the exploration of MUC16- and EDA-targeting therapeutics for the treatment of HGSOC and CEA-targeting agents for MOC.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eEpithelial ovarian carcinoma (EOC), vascular endothelial growth factor (VEGF), Poly (ADP-ribose) polymerase (PARP) inhibitors, high-grade serous OC (HGSOC), CCC (clear-cell carcinoma) and low-grade serous ovarian cancer (LGOC), homologous recombination deficiency (HR-d), spliced extra-domain B (EDB), \u0026nbsp;spliced extra-domain A (EDA), Fibroblast Activation Protein (FAP), cancer-associated fibroblasts (CAFs) , Carcinoembryonic antigen (CEA) , metastatic colorectal cancer (mCRC), Mucinous ovarian cancer (MOC), formalin-fixed, paraffin-embedded (FFPE), immunohistochemistry (IHC), disease-free survival (DFS), overall survival (OS),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin (H\u0026amp;E), wild-type (WT), platinum-free interval (PFI), primary debulking surgery (PDS), Chimeric Antigen Receptor (CAR) T-cells, Mirvetuximab soravtansine (MIRV).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients written informed consent was obtained before the samples collection. This is a no-profit, observational, retrospective study, approved by the Institutional Ethics Committee of \u0026lsquo;Fondazione Policlinico Universitario Agostino Gemelli-IRCCS\u0026rsquo; of Rome, Italy (ID 6144).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and matherials that support the findings of this study are available from the corresponding author upon reasonable request.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD.N. is a co-founder and shareholder of Philogen (www.philogen.com), a Swiss-Italian Biotech company that operates in the field of ligand-based pharmacodelivery. R.D.L., F.P., L.P., and E.P., are employed by Philochem AG, a daughter company of Philogen acting as the discovery unit of the group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eG.S. has been Consultant for Astrazeneca\u0026ndash;MSD, Covidien AG, a Medtronic company, TESARO Bio Italy S.r.l.\u003c/p\u003e\n\u003cp\u003eJohnson \u0026amp; Johnson; he also received as a speaker Bureau/Honoraria from Olympus Europa SE \u0026amp; CO. KG, Baxter Healthcare SA, Intuitive Surgical Inc., GlaxoSmithKline S.p.A, and honoraria/expenses from Clovis Oncology Italy S.r.l. A.F. has been Consultant for Johnson \u0026amp; Johnson SpA, Fondazione Internazionale Menarini, Oncoinvent AS, she also received as a speaker for: GlaxoSmithKline and Covidien/Medtronic, Grant/Researcher Support for AstraZeneca\u0026amp;MSD. She declares relashionship with commercial interest with AstraZeneca/MSD, Johnson \u0026amp; Johnson\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFondazione Internazionale Menarini, GlaxoSmithKline, Oncoinvent AS, Covidien/Medtronic.\u0026nbsp;C.N. received travel support from MSD, Illumina and honoraria as a speaker/advisory board from Veeva, GSK, MSD, AZ, Altems, Illumina. GFZ received as a speaker honoraria GlaxoSmithKline S.p.A. The remaining authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was partially supported by Philogen S.p.a.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA.P., R.D.L., E.P., T.P., C.N., \u0026ldquo;Writing - Original Draft\u0026rdquo;;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA.P., R.D.L.,\u0026nbsp;C.N., \u0026ldquo;Methodology\u0026rdquo;;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA.P., N.D.A, A.T., T.P., D.G., \u0026ldquo;Software\u0026rdquo;, \u0026ldquo;Formal Analysis\u0026rdquo;and\u0026nbsp;\u0026nbsp;\u0026ldquo;Data Curation\u0026rdquo;;\u003c/p\u003e\n\u003cp\u003eM.B., F.S., \u0026quot;Project administration\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eA.P., R.D.L., E.P.,\u0026nbsp;C.N., \u0026ldquo;Investigations\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;F.P., L.P., G.F.Z., A.F., D.N., G.S., \u0026ldquo;supervision\u0026rdquo; and \u0026ldquo;writing\u0026ndash;review and editing\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eAll authors discussed and contributed to the final manuscript, approving the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our gratitude to Dr. Mariagrazia Valentini and Dr. Roberta Benvenuto for technical support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGonz\u0026aacute;lez-Mart\u0026iacute;n A, Harter P, Leary A, Lorusso D, Miller RE, Pothuri B, et al. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(10):833\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiang C, Huang YH, Lu JB, Yang YZ, Rao HL, Zhang B, et al. Perivascular cell coverage of intratumoral vasculature is a predictor for bevacizumab efficacy in metastatic colorectal cancer. Cancer Manag Res. 2018;10:3589\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16(8):928\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaram A, Ledermann JA, Kim JW, Sehouli J, Lu K, Gourley C et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions. Annals of Oncology. 2017;28(4):711\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Q, Peng H, Qi X, Wu M, Zhao X. Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence. Signal Transduct Target Ther. 2020;5(1):137.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColombo N, Sessa C, du Bois A, Ledermann J, McCluggage WG, McNeish I et al. ESMO\u0026ndash;ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Annals of Oncology. 2019;30(5):672\u0026ndash;705.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHooper AT, Marquette K, Chang CPB, Golas J, Jain S, Lam MH, et al. Anti-Extra Domain B Splice Variant of Fibronectin Antibody\u0026ndash;Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade. Mol Cancer Ther. 2022;21(9):1462\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchliemann C, Wiedmer A, Pedretti M, Szczepanowski M, Klapper W, Neri D. Three clinical-stage tumor targeting antibodies reveal differential expression of oncofetal fibronectin and tenascin-C isoforms in human lymphoma. Leuk Res. 2009;33(12):1718\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePedretti M, Soltermann A, Arni S, Weder W, Neri D, Hillinger S. Comparative immunohistochemistry of L19 and F16 in non-small cell lung cancer and mesothelioma: Two human antibodies investigated in clinical trials in patients with cancer. Lung Cancer. 2009;64(1):28\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVilla A, Trachsel E, Kaspar M, Schliemann C, Sommavilla R, Rybak J, et al. A high-affinity human monoclonal antibody specific to the alternatively spliced EDA domain of fibronectin efficiently targets tumor neo‐vasculature \u003cem\u003ein vivo\u003c/em\u003e. Int J Cancer. 2008;122(11):2405\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eViti F, Tarli L, Giovannoni L, Zardi L, Neri D. Increased binding affinity and valence of recombinant antibody fragments lead to improved targeting of tumoral angiogenesis. Cancer Res. 1999;59(2):347\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCalais JFAP. The Next Billion Dollar Nuclear Theranostics Target? J Nucl Med. 2020;61(2):163\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePl\u0026uuml;ss L, Peissert F, Elsayed A, Rotta G, R\u0026ouml;mer J, Dakhel Plaza S et al. Generation and \u003cem\u003ein vivo\u003c/em\u003e characterization of a novel high-affinity human antibody targeting carcinoembryonic antigen. MAbs. 2023;15(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen X, Li X, Wang X, Zhu Q, Wu X, Wang X. MUC16 impacts tumor proliferation and migration through cytoplasmic translocation of P120-catenin in epithelial ovarian cancer cells: an original research. BMC Cancer. 2019;19(1):171.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)\u0026mdash;A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42(2):377\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17(4):343\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. J Am Stat Assoc. 1958;53(282):457\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhai Y, Lu Q, Lou T, Cao G, Wang S, Zhang Z. MUC16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells. Ann Transl Med. 2020;8(22):1494\u0026ndash;1494.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrawford A, Haber L, Kelly MP, Vazzana K, Canova L, Ram P, et al. A Mucin 16 bispecific T cell\u0026ndash;engaging antibody for the treatment of ovarian cancer. Sci Transl Med. 2019;11:497.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErba PA, Sollini M, Orciuolo E, Traino C, Petrini M, Paganelli G, et al. Radioimmunotherapy with Radretumab in Patients with Relapsed Hematologic Malignancies. J Nucl Med. 2012;53(6):922\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeri D. Antibody\u0026ndash;Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity. Cancer Immunol Res. 2019;7(3):348\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, et al. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023;41(13):2436\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ovarian cancer, Extra domain A of fibronectin, Extra domain B of fibronectin, Fibroblast activation protein, Carcinoembryonic Antigen, MUC16, therapeutic antibodies, vascular targeting, targeted therapy","lastPublishedDoi":"10.21203/rs.3.rs-4490240/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4490240/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOvarian cancer is a significant health concern, necessitating the identification of potential diagnostic markers and novel therapeutic targets. This study presents, to the best of our knowledge, the first comparative immunohistochemical analysis of five tumor markers, namely the extra-domains A and B of fibronectin, fibroblast activation protein, carcinoembryonic antigen, and MUC16 in human epithelial ovarian cancer tissue samples.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eFormalin-fixed paraffin-embedded human ovarian tissue sections were stained using previously validated antibodies to assess the percentage and intensity of marker expressions.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOur results indicate a similar stromal pattern of expression for fibroblast activation protein, extra-domains A, and extra-domains B, with extra-domains A exhibiting the most intense staining. MUC16 was abundantly expressed on tumor cells of high-grade serous carcinoma samples, while carcinoembryonic antigen was not detected in this indication. Subsequent staining revealed that carcinoembryonic antigen was highly expressed on mucinous ovarian cancer specimens. With respect to clinical features, MUC16 and extra-domains A were found to be highly expressed in the most challenging scenarios namely platinum-resistant (100% and 50% respectively) and BRCA WT (75% and 45% respectively) patients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe findings of this study highlight that MUC16, extra-domains B, and extra-domains A are attractive targets for the treatment of serous ovarian carcinoma, while carcinoembryonic antigen could be exploited for mucinous ovarian cancer. Clinical investigations are warranted to validate the potential of antibody-based therapies targeting these antigens in the context of ovarian cancer.\u003c/p\u003e","manuscriptTitle":"Identifying New Therapeutic Targets in Epithelial Ovarian Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-26 19:03:39","doi":"10.21203/rs.3.rs-4490240/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba7e07d4-9de9-436d-bbaf-84aeb4759b7e","owner":[],"postedDate":"June 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-01T16:04:03+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-26 19:03:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4490240","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4490240","identity":"rs-4490240","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}