Correlation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary Ovarian Cancer

Correlation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary 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 Correlation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary Ovarian Cancer Huimin Wang, Cong Chen, Danbo Wang, Yanmei Zhu, Peng Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-651274/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: To establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis. Methods: Retrospectively collected clinicopathological and follow-up data of 174 clear cell and endometrial ovarian cancer patients. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer, and comparative analysis of the clinicopathological characteristics and prognosis conducted. Results: Average age and proportion of menopausal patients in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P<0.05). Other clinicopathological features examined, including body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA199, stage, differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1β and Napsin A were not significantly different between the groups (P>0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05). Conclusion: Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy. Surgery Oncology endometriosis-associated ovarian cancer ovarian clear cell carcinoma ovarian endometrioid carcinoma diagnostic criteria Figures Figure 1 Figure 2 Figure 3 1 Background Endometriosis is a common disease in women of childbearing age, with an incidence of 15–20%[ 1 ]. Studies to date have shown that endometriosis has the same molecular biological and genetic background as ovarian cancer and presents a high risk factor for ovarian cancer development[ 2 ]. According to the current internationally recognized Sampson and Scott diagnostic criteria: first,there must be a clear example of endometriosis in association or close proximity to the cancer; secondly,no other primary tumour site must exist and the histology of the tumour must be consistent with an endometrial origin; thirdly,the endometriosis associated with cancers must show a morphologic progression from benign to malignant in a contiguous fashion[ 3 – 4 ], the malignant transformation rate of endometriosis is 0.5–1.0%[ 5 ]. However, due to the significant heterogeneity of endometriosis and atypical hyperplasia, high rates of missed pathological diagnosis, the actual incidence of malignant transformation of endometriosis may be higher[ 6 – 7 ], which presents a challenge in establishing accurate diagnostic criteria. The major pathological types of endometriosis-associated ovarian cancer are endometrioid and clear cell cancers, accounting for 75–90% cases[ 8 ]. However, according to the diagnostic criteria of Sampson and Scott, only 50–70% ovarian clear cell and endometrioid carcinoma cases are diagnosed as endometriosis-associated ovarian cancer(EAOC). According to the theory of external origin of ovarian cancer, clear cell and endometrioid carcinoma types are closely related to endometriosis, potentially resulting from endometriosis-associated malignancy[ 9 ].Our research is focused on the malignant transformation of endometriosis. Previous studies have demonstrated comparable abnormal expression of EAOC-related genes, such as mismatch repair gene human mutL homolog 1(hLMH1) and runt-related transcription factor3(RUNX3), between EAOC and non-endometriosis-associated primary ovarian cancer(non-EAOC) groups[ 10 – 11 ], leading to the speculation that clear cell carcinoma and endometrioid carcinoma of the ovary may be all originate from malignant transformation of endometriosis. Since the pathological changes of endometriosis are heterogeneous, particularly after malignant transformation, tumor tissues grow vigorously and destroy the original tissues, and the histological basis of endometriosis remains unclear; pathological sampling has a number of limitations; cancer and endometriosis lesions are not obtained at the same time, and concurrent endometriosis is often overlooked, resulting in a low diagnostic rate of malignant transformation of endometriosis using the standards of Sampson and Scott. Further relevant clinical and basic research evidence is thus warranted to validate this theory. 2 Materials And Methods (1) Research Objects 174 cases of ovarian clear cell carcinoma and ovarian endometrioid carcinoma were diagnosed and treated in China Medical University Cancer Hospital and Affiliated Shengjing Hospital from January 2008 to November 2018.According to the standards proposed by Sampson and Scott, patients were divided into EAOC group and non-EAOC group, including 74 patients in EAOC group and 100 patients in non-EAOC group.According to different pathological types, the endometriosis associated ovarian clear cell carcinoma (EOCC) group and the endometriosis associated ovarian endometrioid carcinoma (EOEC) group were further divided.The non-endometria-related primary ovarian cancer group was divided into two groups: clear cell carcinoma (OCC) and endometrioid carcinoma (OEC), including 39 EOCC cases, 35 EOECC cases, 35 OCC cases and 65 OECC cases.Samples were fully encoded to protect patient confidentially. Inclusion criteria: 1) Clear pathological diagnosis, limited to clear cell carcinoma and endometrioid carcinoma;2) Complete case data;3) Complete the initial treatment plan (surgery and chemotherapy).Exclusion criteria: 1) Other histological types of ovarian malignancies and ovarian borderline tumors of non-clear cell carcinoma and endometrioid carcinoma;2) Patients with other primary malignant tumors.3) Patients with metastatic ovarian cancer.The samples of the selected cases were rechecked by the same gynaecological pathologist to further confirm the diagnosis. (2) Data Collection Clinicopathological data of all patients were collected.The details are as follows: Clinical data: age;Body Mass Index (BMI), history of menstrual, postmenopausal status, age of menopause, history of surgery, complications, results of related serum tumor markers (CA125, CA199, HE4). Pathological data: tumor size, tumor side, ascites, FIGO stage, histological classification, immunohistochemical results (ER, PR, P53, P16, Ki67, MMR, HNF-1, Napsin A). (3) Treatment All the included patients received standard surgical treatment: patients in the early stage (FIGO I-II) received comprehensive staging surgery, and patients in the advanced stage (FIGO III-IV) received tumor cell reduction surgery.Postoperative chemotherapy regiments containing platinum were adopted according to international guidelines: paclitaxel and carboplatin (TC regimen), docetaxel and carboplatin (DC regimen), 6–8 cycles of chemotherapy, with an interval of 21 days. (4) Follow-up All cases were followed up to the end of recurrence, death or the end of follow-up, up to 31/3/2019, the follow-up time was 6-132 months, and the median time was 67 months.Reoperation to obtain histopathological evidence and/or imaging evidence of new developments and/or continued abnormal elevation of tumor markers is considered to tumor recurrence. (5) Statistical methods The data were analyzed by SPSS 25.0 software.Enumeration data are expressed in terms of rates, Measurement data are expressed as mean ± standard deviation (± s), T test was used for comparison between groups, The enumeration data were compared using the test and Fisher's exact test, survival analysis using Kalan - Meier survival curve and using Log - rank test to compare the difference, P < 0.05 was statistically significant. 3 Results (1) General data analysis In total, 174 cases of clear cell carcinoma and endometrioid carcinoma of the ovary were included, including 74 in the EAOC and 100 in the non-EAOC group. Analysis of epidemiological data revealed lower average age and proportion of menopause of patients in the EAOC group than the non-EAOC group (P 0.05), as shown in Table 1 . Table 1 Comparative analysis of the epidemiological data of EAOC and non-EAOC patients (n,x ± s) Characteristics EAOC Non-EAOC P 74 100 Age(year) 49.4 ± 7.7 54.0 ± 10.0 0.001 BMI 23.6 ± 3.3 23.5 ± 3.7 0.731 History of menstrual 0.064 Yes 29 26 No 55 74 Postmenopausal status 0.001 Yes 32 68 No 42 32 Age of menopause 49.1 ± 4.3 49.3 ± 3.9 0.815 History of surgery 0.115 Yes 19 16 No 65 84 Complications 0.683 Yes 31 45 No 43 55 Further intra-group and inter-group analyses of the same pathological types showed significantly lower average age of onset and proportion of menopause in the EOCC than OCC group (P 0.05; Table 2 ). Table 2 Intra-group and inter-group analyses of EAOC and non-EAOC patients (n,x ± s) Characteristics EOEC EOCC OEC OCC P 35 39 65 35 Age(year) 50.6 ± 8.4 48.2 ± 6.7 54.3 ± 10.7 53.3 ± 8.6 0.177 a /0.060 b / <0.01 c BMI 23.9 ± 2.9 23.3 ± 3.6 23.7 ± 3.8 22.8 ± 3.1 0.430 a /0.782 b /0.570 c History of menstrual 0.076 a /0.667 b /0.075 c Yes 10 19 16 10 No 25 20 49 25 Postmenopausal status 0.178 a /0.199 b / <0.01 c Yes 18 14 42 26 No 17 25 23 9 Age of menopause 48.8 ± 4.7 49.2 ± 3.8 49.9 ± 4.1 48.2 ± 3.2 0.802 a /0.408 b /0.363 c History of surgery 0.599 a /0.106 b /0.810 c Yes 8 11 7 9 No 27 28 58 26 Complications 0.528 a /0.916 b /0.892 c Yes 16 15 29 14 No 19 24 36 21 a:EOEC vs. EOCC, b:EOEC vs. OEC, c:EOCC vs. OCC. (2) Analysis of clinical features No significant differences were evident between the two groups in terms of tumor size, tumor side, ascites, CA125, HE4, and CA199 levels (all P > 0.05). The collective data are presented in Table 3 . Table 3 Comparative analysis of clinical features of EAOC and non-EAOC patients (n,x ± s) Characteristics EAOC Non-EAOC P 74 100 Ascites 0.666 Yes 39 56 No 35 44 Tumor size 0.769 ≥ 10cm 45 63 ༜10cm 29 37 Tumor side 0.355 Unilateral 53 65 Bilateral 21 35 Biomaker CA125(U/ml) 448.9 ± 980.0 739.8 ± 1141.4 0.080 HE4(pmol/L) 203.4 ± 240.0 264.5 ± 217.5 0.620 CA199(U/ml) 194.0 ± 460.4 274.2 ± 546.7 0.465 Further intra-group and inter-group analyses disclosed significantly higher incidence of bilateral tumors in the EOEC than EOCC group (40.0% vs 17.9%, P < 0.05). Moreover, the HE4 level in the EOEC group was higher than that in the EOCC group to a significant extent (355.4 vs 89.4 pmol/L, P < 0.05). No significant differences were found in the remaining parameters (Table 4). tumor size, tumor side;Ascites;FIGO staging.Histological classification (3)Pathological characteristics Pathological characteristics were comparable between the two groups in terms of FIGO stage, differentiation degree, ER, PR, P53, P16, Ki67, MMR, hnf-1, and Napsin A-positive expression (all P > 0.05; Table 5 , Fig. 1 ). TABL 4 Intra-group and inter-group clinical features analyses of EAOC and non-EAOC patients (n，x±s） Characteristics EOEC EOCC OEC OCC P 35 39 65 35 Ascites 0.469 a /0.295 b /0.209 c Yes 20 19 44 12 No 15 20 21 23 Tumor size 0.892 a /0.881 b /0.363 c ≥10cm 21 24 38 25 ＜10cm 14 15 27 10 Tumor side 0.036 a /0.303 b /0.316 c Unilateral 21 32 33 32 Bilateral 14 7 32 3 Biomaker CA125（U/ml） 618.0±1309.8 297.0±509.6 870.3±895.0 493.7±1479.0 0.161 a /0.255 b /0.437 c HE4（pmol/L） 355.4±319.5 89.4±69.1 498.9±547.0 132.7±259.0 0.039 a /0.575 b /0.651 c CA199（U/ml） 248.1±525.4 160.6±423.0 276.9±586.0 220.5±547.0 0.556 a /0.877 b /0.663 c a:EOEC vs. EOCC, b:EOEC vs. OEC, c:EOCC vs. OCC. Table 5 Comparative analysis of pathological characteristics of EAOC and non-EAOC patients(n,%) Characteristics EAOC Non-EAOC P 74 100 FIGO stage 0.417 I/II 51 63 III/IV 23 37 Differentiation 0.932 Low 18 21 Middle 34 52 High 22 27 Biomarker ER(+) 32 52 0.253 PR(+) 24 45 0.094 P53(+) 59 68 0.085 P16(+) 41 54 0.854 MMR(-) 19 37 0.114 Ki67(%) 30.0 ± 18.0 30.8 ± 18.94 0.767 Napsin A(+) 18 37 0.075 HNF-1β(+) 15 31 0.113 The rates of ER and PR positivity in the EOEC group were significantly higher than those in the EOCC group (71.4% vs. 17.9%, 60.0% vs. 7.7%; P < 0.05). Conversely, the rates of HNF-1 and Napsin A positivity in the EOCC group were significantly higher relative to the EOEC group (28.2% vs. 20.0%, 30.8% vs. 7.7%; P < 0.05). HNF-1 and Napsin A positive rates in the OCC group were significantly higher than those in the OEC group (74.2% vs. 16.9%, 80.0% vs. 4.6%; P < 0.05), as shown in Table 6 . Table 6 Intra-group and inter-group pathological characteristics of EAOC and non-EAOC patients(n,%) Characteristics EOEC EOCC OEC OCC P 35 39 65 35 FIGO stage I/II 21 30 37 26 0.116 a /0.767 b /0.792 c III/IV 14 9 28 9 Differentiation Low 11 7 18 3 0.177 a /0.695 b /0.239 c Middle 17 17 40 12 High 7 15 7 20 Biomarker ER(+) 25 7 49 3 < 0.01 a /0.667 b /0.311 c PR(+) 21 3 40 5 < 0.01 a /0.880 b /0.635 c P53(+) 29 30 43 25 0.526 a /0.076 b /0.589 c P16(+) 16 25 32 22 0.112 a /0.710 b /0.912 c MMR(-) 8 11 22 15 0.072 a /0.548 b /0.291 c Ki67(%) 29.1 ± 20 30.7 ± 14 29.6 ± 19 33.0 ± 16.5 0.718 a /0.907 b /0.564 c Napsin A(+) 7 11 11 26 < 0.01 a /0.459 b /0.230 c HNF-1β(+) 3 12 3 28 < 0.01 a /0.317 b /0.273 c a:EOEC vs. EOCC, b:EOEC vs. OEC, c:EOCC vs. OCC. (4) Prognostic characteristics Overall, 74 patients in the EAOC group were subjected to initial analyses, 64 of whom were followed up (follow-up rate of 86.5%). Rates of platinum therapy resistance, recurrence and mortality were determined as 6.25%, 39.1%, and 28.1%, respectively. Among the 100 patients in the non-EAOC group, 85 were followed up (85.0%). The platinum resistance rate was determined as 9.41%, recurrence rate as 54.1%, and mortality rate as 40.0%, which were not significantly different between the two groups (all P > 0.05; Table 7 ). Table 7 Prognosis comparison between EAOC and non-EAOC patients(n) Characteristics EAOC non-EAOC P 74 100 Platinum resistance 4 8 0.483 Relapse 25 39 0.405 Death 19 34 0.193 Kaplan-Meier analysis and log-rank test showed that the average overall survival (OS) of the EAOC group was 91.6 months (95% CI: 76.9–106.5 months) while that of the non-EAOC group was 77.8 months (95% CI: 66.1–90.0 months), with no significant differences (P = 0.068, > 0.05). The median progression-free survival (PFS) of the EAOC group was 78.4 months (95% CI: 62.2–94.5 months), which was not significantly different from the non-EAOC group (64.0 months; 95% CI: 50.7–77.1 months) (P = 0.216, > 0.05), as shown in Fig. 2 . Intra-group and inter-group analyses of the same pathological types via Kaplan-Meier and log-rank tests showed that OS of the EOCC group was 90.8 months (95% CI, 69.9–111.8 months), EOEC group was 96.8 months (95% CI, 76.8–116.8 months), OCC group was 77.4 months (95% CI, 51.49–103.30 months), and OEC group was 81.10 months (95% CI, 68.0–94.2 months). We observed no significant differences in OS in EOCC vs. EOEC, EOCC vs. OCC, and EOEC vs. OEC groups (P = 0.290, 0.262, 0.070, all P > 0.05). PFS of patients in the EOCC group was 80.9 months (95% CI, 61.2–100.6 months), EOEC group was 82.3 months (95% CI 59.4–105.2 months), OCC group was 85.9 months (95% CI 68.4–108.3 months), and OEC group was 60.0 months (95% CI 45.50–74.6 months). We observed no significant differences in PFS in EOCC vs EOEC, EOCC vs OCC, and EOEC vs OEC groups (P = 0.222, 0.675, 0.071, all P > 0.05; Fig. 3 ). 4 Discussion Several recent studies have shown that endometriosis patients have significantly increased risk of ovarian cancer[ 12 ]. As a precancerous lesion, endometriosis is closely related to ovarian clear cell and endometrioid carcinomas. The theory of external origin of ovarian cancer hypothesizes that both clear cell and endometrioid carcinoma of the ovary originate from malignant transformation of endometriosis, which poses a challenge to the current diagnostic criteria for malignant transformation of endometriosis. However, further clinical and basic research evidence is needed to substantiate this theory. In the current study, the two ovarian cancer types(ovarian clear cell carcinoma and ovarian endometrioid carcinoma) most closely associated with endometriosis were examined as a whole. According to the diagnostic criteria of Sampson and Scott, samples were divided into EAOC and non-EAOC groups, and clinicopathologic features and prognosis between the groups compared. Our results showed no significant differences between the groups, supporting the theory that both non-endometriosis-associated primary ovarian endometrial carcinoma and ovarian clear cell carcinoma potentially have the same origin as EAOC from endometriosis. We retrospectively analyzed the clinical features of 174 patients from EAOC and non-EAOC groups. The average age and proportion of menopausal patients in the EAOC group was lower than the non-EAOC group (P < 0.05). The differences may be attributed to a potential drop in postmenopausal hormone levels, gradual atrophic degradation of ectopic endometrium[ 13 ], limitations of pathological materials, and errors due to insufficient pathological evidence of endometriosis, but further experiments on larger sample sizes are required to confirm these findings. No significant differences were evident in BMI, dysmenorrhea history, surgical history, complications, ascites, tumor size and relevant serum tumor markers (CA125, HE4, CA199) between the two groups (all P > 0.05), consistent with earlier results. Our experiments support similar characteristics of endometriosis-associated and non-endometriosis-associated primary ovarian cancers. Furthermore, upon stratified analysis according to pathological type into EOCC and EOEC, OCC and OEC groups, relevant epidemiological and clinical characteristics, such as BMI, dysmenorrhea history, history of surgery, complications, ascites, tumor size and serum tumor marker (CA125, HE4, CA199) levels were not significantly different (P > 0.05). Our findings provide further evidence that primary ovarian endometrial carcinoma and clear cell carcinoma are associated with corresponding pathological types in endometriosis-associated ovarian cancer, with similar clinical features. Histopathology evaluation is the gold standard of ovarian cancer diagnosis and classification. Immunohistochemical analysis revealed high expression of ER and PR in endometrioid carcinoma of ovary and low expression in clear cell carcinoma[ 14 ]. Compared with other epithelial ovarian cancer types, the characteristics of ovarian clear cell carcinoma included HNF-1β increase, high expression of Napsin A and positive expression of P53[ 15 ]. MMR expression in ovarian endometrial carcinoma and clear cell carcinoma is abnormally higher than that in other subtypes of ovarian cancer[ 16 ]. The above molecules are therefore useful as biomarkers to distinguish epithelial ovarian cancer subtypes. Ki-67 is currently used as a positive nuclear proliferation marker and its expression reflects the biological behavior of tumor cells[ 17 ]. For analysis of differences, similarities and potential mechanisms of EAOC and non-EAOC, we compared the pathologies of the two groups. Our data showed no histological differences in terms of pathologic differentiation degree, ER, PR, P53, and P16, Ki67, MMR, HNF-1β and Napsin A-positive expression (P > 0.05) between EAOC and non-EAOC groups.The majority of previous reports have focused on the malignant transformation of endometriosis and few studies have been conducted on the characteristics of different pathological types of endometrial carcinoma and clear cell carcinoma. However, there are a number of specific differences in clinicopathological characteristics between endometrioid and clear cell carcinoma types. Further grouping analysis revealed no significant differences in expression of relevant non-specific indicators, such as P53, P16, Ki67 and MMR, among the groups. The positive expression rates of ER and PR were markedly different between endometrioid carcinoma and clear cell carcinoma groups, but not from the primary ovarian carcinoma of the same pathologic type. Differentiation of endometriosis into two tissue types is reported to occur in a dual mode regulated by sex hormones [ 18 – 19 ]: (1) estrogen and progesterone receptor-positive endometriosis lesions undergo malignant transformation to form hormone-dependent endometrioid carcinoma after long-term stimulation without antagonistic estrogen and (2) atrophic ectopic endometrial lesions negative for estrogen and progesterone receptors are stimulated by oxidative stress for a long period of time, resulting in malignant transformation and formation of non-hormone-dependent clear cell carcinoma. The results of this study were consistent with earlier literature, validating that clear cell carcinoma is a non-hormone-dependent tumor. The positive expression rates for HNF-1β and Napsin A were significantly higher in the clear cell carcinoma than endometrioid carcinoma group. Accordingly, we conclude that different histological types undergo distinct mechanisms for development of endometriosis-associated ovarian cancer, which will be the focus of follow-up investigations. The majority of previous studies focused on comparing clinicopathological and prognostic differences between intrauterine endometriosis-associated ovarian cancers of a single pathologic type. However, sample sizes were usually small and the results obtained were inconsistent. Some findings suggest that ovarian endometrial carcinoma and ovarian clear cell carcinoma are early phases with better prognosis than the two pathological types of primary ovarian cancer[ 20 – 21 ], while other researchers have reported no obvious differences[ 22 – 23 ]. Here, we examined 174 cases of ovarian endometrial carcinoma and clear cell carcinoma, with a median follow-up period of 67 months. Our data showed that platinum resistance, recurrence and mortality rates between the EAOC and non-EAOC groups were not significantly different (P > 0.05). PFS and OS were comparable between the two groups (P > 0.05), supporting similar prognosis of EAOC and non-EAOC. In 2020, Marjolein Hermens [ 24 ] analyzed 32,419 patients with ovarian cancer and found synchronous endometriosis of ovarian cancer staging of early, higher survival and overall survival is longer, perhaps because of more frequent hospital visits of patients with endometriosis due to simultaneous treatment with endometriosis drugs, long-term state of inflammation caused by endometriosis, which activates immune function, in turn, leading to early detection and better prognosis, giving rise to the theory that ovarian cancer with endometriosis may have different pathophysiological features to other ovarian cancer types.Earlier studies have established a low early incidence of epithelial ovarian cancer. In this research, early incidence rates of EAOC and non-EAOC were 68.9% and 63.0%, respectively, which were significantly higher than the average early incidence of ovarian cancer (30.0%). Overall survival rates of the EAOC and non-EAOC groups were 71.9% and 60.0%, which were significantly higher than the average five-year survival rate of ovarian epithelial carcinoma (44%- 50%)[ 25 ]. Further indicates that ovarian clear cell carcinoma and endometrioid carcinoma are sources of malignant transformation of endometriosis, therefore can be detected early. But accelerated growth of tumor tissue destroys the tissue of origin because of malignant transformation,pathological materials can not remove cancer and ectopic foci lesions at the same time, consequently, a proportion of clear cell and endometrioid carcinomas of the ovary are not diagnosed as endometriosis-associated ovarian cancer. In summary, no obvious clinicopathological differences between EAOC and non-EAOC were observed in this study, leading to the speculation that primary ovarian endometrial and clear cell carcinoma have the same origin with EAOC. Our findings support the theory of dualism of ovarian cancer that endometrial carcinoma and clear cell carcinoma originate from progression of ovarian endometriosis. Therefore, it is worth exploring whether the stringent diagnostic criteria for malignant transformation of endometriosis require revision. However, the retrospective nature of this study is a limitation, and further large-scale, prospective multicenter clinical and molecular biology studies are required to verify the associations of malignant transformation of endometriosis with ovarian clear cell and endometrial carcinomas, which should aid in clarifying the biological mechanisms and developing individualized treatments for patients with endometriosis-associated ovarian cancer. Abbreviations EAOC endometriosis-associated ovarian cancer non-EAOC non-endometriosis-associated primary ovarian cancer EOCC endometriosis associated ovarian clear cell carcinoma EOEC endometriosis associated ovarian endometrioid carcinoma OCC clear cell carcinoma OEC endometrioid carcinoma BMI Body Mass Index OS overall survival PFS progression-free survival Declarations Ethics approval and consent to participate: Samples were fully encoded to protect patient confidentially. The study and its protocols were approved by the Research Ethics committees of Liaoning Cancer Hospital & Institute (2020G0322). Consent for publication : Not applicable. Availability of data and materials: Not applicable. Competing interests: The authors declare that they have no conflict of interest. Funding: This work was supported by grants from The National Natural Science Foundation of China, Grant Number:81771556. Authors' contributions: HW and CC carried out most parts of the experiment; YZ participated in the experiment; DW participated in the design of the study; HW, CC and PC performed the statistical analysis. All authors read and approved the final manuscript. Acknowledgements: Not applicable References Giudice LC. Endometriosis. N Engl J Med. 2010;362:2389–98. doi: 10.1056/NEJMcp1000274 . Erzen M, Rakar S, Klancnik B, Syrjänen K. Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol. 2001;83:100–8. doi: 10.1006/gyno.2001.6382 . Sampson J. Endometrial carcinoma of the ovary arising in endo metrial tissue in that organ. Arch Surg. 1925;10:1–72. Scott R. Malignant change in endometriosis. Obstet Gynecol. 1953;2:293–9. Swiersz LM. Role of endometriosis in cancer and tumor development. Ann NY Acad Sci. 2002;955:281–92. doi: 10.1111/j.1749-6632.2002.tb02788.x . Gadducci A, Lanfredini N, Tana R. Novel insights on the malignant transformation of endometriosis into ovarian carcinoma. Gynecol Endocrino. 2014;30:612–7. doi: 10.3109/09513590.2014.926325 . Vercellini P, Viganò P, Buggio L, Makieva S, Scarfone G, Cribiù FM, Parazzini F, Somigliana E. Perimenopausal management of ovarian endometriosis and associated cancer risk:When is medical or surgical treatment indicated?Best practice and research. Clin Obstetri Gynaecol. 2018;51:151–68. doi: 10.1016/j.bpobgyn.2018.01.017 . Bas-Esteve E, Pérez-Arguedas M, Guarda-Muratori GA, Acién M, Acién P. Endometriosis and ovarian cancer:Their association and relationship.Eur J Obstet Gynecol Reprod Biol X. 3(2019)100053. doi: 10.1016/j.eurox.2019.100053 . Mallen A, Soong TR, Townsend MK, Wenham RM, Crum CP, Tworoger SS. Surgical prevention strategies in ovarian cancer. Gynecol Oncol. 2018;151:166–75. doi: 10.1016/j.ygyno.2018.08.005 . Ren F, Wang D, Jiang Y. Fengyan Ren.Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis.Arch Gynecol Obstet. 285(2012)215–221. doi: 10.1007/s00404-011-1922-x . Guo C, Ren F, Wang D, Li Y, Liu K, Liu S, Chen P. RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis. Oncology Reports. 2014;32:2580–8. doi: 10.3892/or.2014.3524 . Eleftherios P, Samartzis SI, Labidi-Galy M, Moschetta M, Uccello, Dimitrios R, Kalaitzopoulos JA, Perez-Fidalgo. Stergios Boussios. Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review. Ann Transl Med. 2020;8:1712. doi: 10.21037/atm-20-3022a . Wang S, Qiu L, Lang JH, Shen K, Yang JX, Huang HF, Pan LY, Wu M. Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis. Am J Obstet Gynecol. 2013;208:411–5. doi: 10.1016/j.ajog.2012.12.004 . Chen S, Dai X, Gao Y, Shen F, Ding J. Qi Chen.The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer.Sci Rep. 7(2017) 16922. doi: 10.1038/s41598-017-17265-6 . Philip PC, Ip S-Y, Wang, Oscar GW, Wong K-L, Chow HHok-Yeung, Lee, Annie NY, Cheung K-Y. Tse. Napsin A, Hepatocyte Nuclear Factor-1-Beta (HNF-1β), Estrogen and Progesterone Receptors Expression in Arias-Stella Reaction. Am J Surg Pathol. 2019;43:325–33. doi: 10.1097/PAS.0000000000001212 . Jennifer A, Bennett V, Morales-Oyarvide S, Campbell TA, Longacre EO. Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. Am J Surg Pathol. 2016;40:656–63. doi: 10.1097/PAS.0000000000000602 . Munjishvili V, Barabadze E, Musashvili T, Gachechiladze M, Burkadze G. Morphophenotypic Characteristics of Ovarian Serous Borderline Tumors. Georgian Med News. 2019;290:20–5. Fumihiko Suzuki J-I, Akahira I, Miura T, Suzuki K, Ito S-I, Hayashi H, Sasano N, Yaegashi. Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5’-untranslated region in human epithelial ovarian carcinoma. Cancer Sci. 2008;99:2365–72. doi: 10.1111/j.1349-7006.2008.00988.x . Tanase Y, Yamada Y, Shigetomi H, Kajihara H, Oonogi A, Yoshizawa Y, Furukawa N, Haruta S, Yoshida S, Sado T, Oi H, Kobayashi H. Modulation of estrogenic action in clear cell carcinoma of the ovary. Exp Ther Med. 2012;3:18–24. doi: 10.3892/etm.2011.376 . Ren T, Wang S, Sun J, Qu JM, Xiang Y, Shen K, Lang JH. Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma. J Ovarian Res. 2017;10:67. doi: 10.1186/s13048-017-0363-y . Park JY, Kim DY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH. Significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma. Int J Gynecol Cancer. 2018;28:11–8. doi: 10.1097/IGC.0000000000001136 . Li Q, Sun Y, Zhang X, Wang L, Wu W, Wu M, Meng C, Liu G. Endometriosis-associated ovarian cancer is a single entity with distinct clinicopathological characteristics. Cancer Biol Ther. 2019;20:1029–34. doi: 10.1080/15384047.2019.1595278 . Zhao T, Shao Yu, Liu Y, Wang X, Guan L, Lu Y. Endometriosis does not confer improved prognosis in ovarian clear cell carcinoma: a retrospective study at a single institute. J Ovarian Res. 2018;11:53. doi: 10.1186/s13048-018-0425-9 . Marjolein Hermens, Anne M, van Altena M, van der Aa J, Bulten, Huib AAM, van Vliet AG, Siebers, Ruud LM, Bekkers. Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women. Am J Obstet Gynecol. 2021;224:284.e1-284.e10. doi: 10.1016/j.ajog.2020.08.056 . Moufarrij S, Dandapani M, Arthofer E, Gomez S, Srivastava A, Lopez-Acevedo M, Villagra A, Chiappinelli KB. Epigenetic therapy for ovarian cancer: promise and progress.Clin Epigenetics.11(2019):7. doi: 10.1186/s13148-018-0602-0 . 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-651274","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":35619382,"identity":"114527fa-37dc-45f6-9b60-b30a0703f8ed","order_by":0,"name":"Huimin Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYJACZgYGCQY2BuYDBxIqbHj42RuI1sKW+ODBmTQZyZ4DRGkBAR5jw4cth20MbjjgV25w/Ozh14VtFtF80g1mEokN53kYbjAwfviYg0fLmbw065ltErltMgfSJBJ33OZhnN3ALDlzG24tZgdyzIx5QVokEo5JJJ65zcMsc4CNmReflvNvYFoSQegcD5tEAgEtN3KMH0O0JDMbJLYd4OEhpMX+xhszZp5zIC1pjA8SziTzSPAcbMbrF8n+HOPPPGV1ufNn5H84+KPCzt7+ePPBDx/xaAECNgk0AcYGvOqBgPkDIRWjYBSMglEwwgEAGIdTIABOSTYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-2363-4957","institution":"Liaoning Cancer Institute and Hospital","correspondingAuthor":true,"prefix":"","firstName":"Huimin","middleName":"","lastName":"Wang","suffix":""},{"id":35619383,"identity":"0e8134fe-c6d9-4f06-b349-c9abac0a38bc","order_by":1,"name":"Cong Chen","email":"","orcid":"","institution":"Liaoning Cancer Institute and Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cong","middleName":"","lastName":"Chen","suffix":""},{"id":35619384,"identity":"666b3d84-8e55-492f-b761-4ac1b7da1c13","order_by":2,"name":"Danbo Wang","email":"","orcid":"","institution":"Liaoning Cancer Institute and Hospital","correspondingAuthor":false,"prefix":"","firstName":"Danbo","middleName":"","lastName":"Wang","suffix":""},{"id":35619385,"identity":"b47030f7-8188-4477-9a12-bc0f954560a7","order_by":3,"name":"Yanmei Zhu","email":"","orcid":"","institution":"Liaoning Cancer Institute and Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanmei","middleName":"","lastName":"Zhu","suffix":""},{"id":35619386,"identity":"dd250277-5f14-4b62-a870-783a7bb059f2","order_by":4,"name":"Peng Chen","email":"","orcid":"","institution":"Liaoning Cancer Institute and Hospital","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2021-06-23 09:36:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-651274/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-651274/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":10878413,"identity":"87932f91-165c-4c7d-be9a-ef9f769317f7","added_by":"auto","created_at":"2021-06-28 18:27:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":675496,"visible":true,"origin":"","legend":"The expression of ER、PR、P53、P16、Ki67、MMR、HNF-1β、Napsin A in tissue(SP 200X). 1.ER-positive;2.ER-negative;3.PR-positive;4.PR-negative; 5.P53-positive;6.P53-negative;7.P16-positive;8.P16-negative;9.Ki67-positive;10.Ki67-negative;11.MLH1-positive;12.MLH1-negative;13.MSH2-positive;14.MSH2-negative;15.MSH6-positive;16.MSH6-negative;17.PMS2-positive;18.PMS2-negative;19.HNF-1β-positive;20.HNF-1β-negative;21.Napsin A-positive;22.Napsin A-negative","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-651274/v1/1a624f5cecd2968fa321369b.png"},{"id":10878412,"identity":"2e418ab6-c5e8-4647-8e33-8bf0c02f1ae7","added_by":"auto","created_at":"2021-06-28 18:27:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":19943,"visible":true,"origin":"","legend":"The differences of OS and PFS between EAOC and non-EAOC patients.","description":"","filename":"OnlineFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-651274/v1/d18504b9b921eb8a34a22fd0.png"},{"id":10878279,"identity":"8b7d9901-29d7-439d-bff0-61c608542f76","added_by":"auto","created_at":"2021-06-28 18:24:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":28803,"visible":true,"origin":"","legend":"OS and PFS differences of EOCC vs. EOEC、EOCC vs. OCC、EOEC vs. OEC.","description":"","filename":"OnlineFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-651274/v1/7baec814b0ae91a1683b779d.png"},{"id":14361682,"identity":"4953e8e2-c20f-49bc-be28-db9c37a3955d","added_by":"auto","created_at":"2021-10-08 21:49:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":525031,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-651274/v1/bd267f0b-344f-45b7-ae09-1ece40380f22.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eCorrelation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary Ovarian Cancer\u003c/p\u003e","fulltext":[{"header":"1 Background","content":" \u003cp\u003eEndometriosis is a common disease in women of childbearing age, with an incidence of 15\u0026ndash;20%[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Studies to date have shown that endometriosis has the same molecular biological and genetic background as ovarian cancer and presents a high risk factor for ovarian cancer development[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. According to the current internationally recognized Sampson and Scott diagnostic criteria: first,there must be a clear example of endometriosis in association or close proximity to the cancer; secondly,no other primary tumour site must exist and the histology of the tumour must be consistent with an endometrial origin; thirdly,the endometriosis associated with cancers must show a morphologic progression from benign to malignant in a contiguous fashion[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], the malignant transformation rate of endometriosis is 0.5\u0026ndash;1.0%[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, due to the significant heterogeneity of endometriosis and atypical hyperplasia, high rates of missed pathological diagnosis, the actual incidence of malignant transformation of endometriosis may be higher[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], which presents a challenge in establishing accurate diagnostic criteria.\u003c/p\u003e \u003cp\u003eThe major pathological types of endometriosis-associated ovarian cancer are endometrioid and clear cell cancers, accounting for 75\u0026ndash;90% cases[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, according to the diagnostic criteria of Sampson and Scott, only 50\u0026ndash;70% ovarian clear cell and endometrioid carcinoma cases are diagnosed as endometriosis-associated ovarian cancer(EAOC). According to the theory of external origin of ovarian cancer, clear cell and endometrioid carcinoma types are closely related to endometriosis, potentially resulting from endometriosis-associated malignancy[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].Our research is focused on the malignant transformation of endometriosis. Previous studies have demonstrated comparable abnormal expression of EAOC-related genes, such as mismatch repair gene human mutL homolog 1(hLMH1) and runt-related transcription factor3(RUNX3), between EAOC and non-endometriosis-associated primary ovarian cancer(non-EAOC) groups[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], leading to the speculation that clear cell carcinoma and endometrioid carcinoma of the ovary may be all originate from malignant transformation of endometriosis. Since the pathological changes of endometriosis are heterogeneous, particularly after malignant transformation, tumor tissues grow vigorously and destroy the original tissues, and the histological basis of endometriosis remains unclear; pathological sampling has a number of limitations; cancer and endometriosis lesions are not obtained at the same time, and concurrent endometriosis is often overlooked, resulting in a low diagnostic rate of malignant transformation of endometriosis using the standards of Sampson and Scott. Further relevant clinical and basic research evidence is thus warranted to validate this theory.\u003c/p\u003e "},{"header":"2 Materials And Methods","content":" \u003cp\u003e(1) Research Objects\u003c/p\u003e \u003cp\u003e174 cases of ovarian clear cell carcinoma and ovarian endometrioid carcinoma were diagnosed and treated in China Medical University Cancer Hospital and Affiliated Shengjing Hospital from January 2008 to November 2018.According to the standards proposed by Sampson and Scott, patients were divided into EAOC group and non-EAOC group, including 74 patients in EAOC group and 100 patients in non-EAOC group.According to different pathological types, the endometriosis associated ovarian clear cell carcinoma (EOCC) group and the endometriosis associated ovarian endometrioid carcinoma (EOEC) group were further divided.The non-endometria-related primary ovarian cancer group was divided into two groups: clear cell carcinoma (OCC) and endometrioid carcinoma (OEC), including 39 EOCC cases, 35 EOECC cases, 35 OCC cases and 65 OECC cases.Samples were fully encoded to protect patient confidentially.\u003c/p\u003e \u003cp\u003eInclusion criteria: 1) Clear pathological diagnosis, limited to clear cell carcinoma and endometrioid carcinoma;2) Complete case data;3) Complete the initial treatment plan (surgery and chemotherapy).Exclusion criteria: 1) Other histological types of ovarian malignancies and ovarian borderline tumors of non-clear cell carcinoma and endometrioid carcinoma;2) Patients with other primary malignant tumors.3) Patients with metastatic ovarian cancer.The samples of the selected cases were rechecked by the same gynaecological pathologist to further confirm the diagnosis.\u003c/p\u003e \u003cp\u003e(2) Data Collection\u003c/p\u003e \u003cp\u003eClinicopathological data of all patients were collected.The details are as follows:\u003c/p\u003e \u003cp\u003eClinical data: age;Body Mass Index (BMI), history of menstrual, postmenopausal status, age of menopause, history of surgery, complications, results of related serum tumor markers (CA125, CA199, HE4).\u003c/p\u003e \u003cp\u003ePathological data: tumor size, tumor side, ascites, FIGO stage, histological classification, immunohistochemical results (ER, PR, P53, P16, Ki67, MMR, HNF-1, Napsin A).\u003c/p\u003e \u003cp\u003e(3) Treatment\u003c/p\u003e \u003cp\u003eAll the included patients received standard surgical treatment: patients in the early stage (FIGO I-II) received comprehensive staging surgery, and patients in the advanced stage (FIGO III-IV) received tumor cell reduction surgery.Postoperative chemotherapy regiments containing platinum were adopted according to international guidelines: paclitaxel and carboplatin (TC regimen), docetaxel and carboplatin (DC regimen), 6\u0026ndash;8 cycles of chemotherapy, with an interval of 21 days.\u003c/p\u003e \u003cp\u003e(4) Follow-up\u003c/p\u003e \u003cp\u003eAll cases were followed up to the end of recurrence, death or the end of follow-up, up to 31/3/2019, the follow-up time was 6-132 months, and the median time was 67 months.Reoperation to obtain histopathological evidence and/or imaging evidence of new developments and/or continued abnormal elevation of tumor markers is considered to tumor recurrence.\u003c/p\u003e \u003cp\u003e(5) Statistical methods\u003c/p\u003e \u003cp\u003eThe data were analyzed by SPSS 25.0 software.Enumeration data are expressed in terms of rates, Measurement data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (\u0026plusmn;\u0026thinsp;s), T test was used for comparison between groups, The enumeration data were compared using the test and Fisher's exact test, survival analysis using Kalan - Meier survival curve and using Log - rank test to compare the difference, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was statistically significant.\u003c/p\u003e "},{"header":"3 Results","content":"\u003cp\u003e(1) General data analysis\u003c/p\u003e\n\u003cp\u003eIn total, 174 cases of clear cell carcinoma and endometrioid carcinoma of the ovary were included, including 74 in the EAOC and 100 in the non-EAOC group. Analysis of epidemiological data revealed lower average age and proportion of menopause of patients in the EAOC group than the non-EAOC group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant differences in BMI, dysmenorrhea history, menopausal age, surgical history, and complications were observed between the two groups (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparative analysis of the epidemiological data of EAOC and non-EAOC patients (n,x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-EAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e74\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(year)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.731\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory of menstrual\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.064\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostmenopausal status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge of menopause\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.815\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory of surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.115\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e84\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComplications\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.683\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eFurther intra-group and inter-group analyses of the same pathological types showed significantly lower average age of onset and proportion of menopause in the EOCC than OCC group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). We observed no marked differences in the remaining parameters between the groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eIntra-group and inter-group analyses of EAOC and non-EAOC patients (n,x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEOEC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEOCC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOEC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOCC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e39\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e65\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(year)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.177\u003csup\u003ea\u003c/sup\u003e/0.060\u003csup\u003eb\u003c/sup\u003e/\u003cstrong\u003e\u0026lt;0.01\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.430\u003csup\u003ea\u003c/sup\u003e/0.782\u003csup\u003eb\u003c/sup\u003e/0.570\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory of menstrual\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.076\u003csup\u003ea\u003c/sup\u003e/0.667\u003csup\u003eb\u003c/sup\u003e/0.075\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePostmenopausal status\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.178\u003csup\u003ea\u003c/sup\u003e/0.199\u003csup\u003eb\u003c/sup\u003e/\u003cstrong\u003e\u0026lt;0.01\u003c/strong\u003e\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge of menopause\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.802\u003csup\u003ea\u003c/sup\u003e/0.408\u003csup\u003eb\u003c/sup\u003e/0.363\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistory of surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.599\u003csup\u003ea\u003c/sup\u003e/0.106\u003csup\u003eb\u003c/sup\u003e/0.810\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComplications\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.528\u003csup\u003ea\u003c/sup\u003e/0.916\u003csup\u003eb\u003c/sup\u003e/0.892\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003ea:EOEC \u003cem\u003evs.\u003c/em\u003e EOCC, b:EOEC \u003cem\u003evs.\u003c/em\u003e OEC, c:EOCC \u003cem\u003evs.\u003c/em\u003e OCC.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e(2) Analysis of clinical features\u003c/p\u003e\n\u003cp\u003eNo significant differences were evident between the two groups in terms of tumor size, tumor side, ascites, CA125, HE4, and CA199 levels (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The collective data are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparative analysis of clinical features of EAOC and non-EAOC patients (n,x\u0026thinsp;\u0026plusmn;\u0026thinsp;s)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-EAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e74\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAscites\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.666\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTumor size\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.769\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ge;\u0026thinsp;10cm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e༜10cm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTumor side\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.355\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUnilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBiomaker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCA125(U/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e448.9\u0026thinsp;\u0026plusmn;\u0026thinsp;980.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e739.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1141.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.080\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHE4(pmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e203.4\u0026thinsp;\u0026plusmn;\u0026thinsp;240.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e264.5\u0026thinsp;\u0026plusmn;\u0026thinsp;217.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.620\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCA199(U/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e194.0\u0026thinsp;\u0026plusmn;\u0026thinsp;460.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e274.2\u0026thinsp;\u0026plusmn;\u0026thinsp;546.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.465\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eFurther intra-group and inter-group analyses disclosed significantly higher incidence of bilateral tumors in the EOEC than EOCC group (40.0% vs 17.9%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Moreover, the HE4 level in the EOEC group was higher than that in the EOCC group to a significant extent (355.4 vs 89.4 pmol/L, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant differences were found in the remaining parameters (Table\u0026nbsp;4). tumor size, tumor side;Ascites;FIGO staging.Histological classification\u003c/p\u003e\n\u003cp\u003e(3)Pathological characteristics\u003c/p\u003e\n\u003cp\u003ePathological characteristics were comparable between the two groups in terms of FIGO stage, differentiation degree, ER, PR, P53, P16, Ki67, MMR, hnf-1, and Napsin A-positive expression (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTABL 4\u003c/strong\u003e Intra-group and inter-group clinical features analyses of EAOC and non-EAOC patients (n，x\u0026plusmn;s）\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"118\"\u003e\n\u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u003cstrong\u003eEOEC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003eEOCC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003eOEC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u003cstrong\u003eOCC\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"146\"\u003e\n\u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003e39\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u003cstrong\u003e65\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eAscites\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e0.469\u003csup\u003ea\u003c/sup\u003e/0.295\u003csup\u003eb\u003c/sup\u003e/0.209\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eTumor size\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e0.892\u003csup\u003ea\u003c/sup\u003e/0.881\u003csup\u003eb\u003c/sup\u003e/0.363\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003e\u0026ge;10cm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003e＜10cm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eTumor side\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.036\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e/0.303\u003csup\u003eb\u003c/sup\u003e/0.316\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eUnilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eBiomaker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eCA125（U/ml）\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e618.0\u0026plusmn;1309.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e297.0\u0026plusmn;509.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e870.3\u0026plusmn;895.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e493.7\u0026plusmn;1479.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e0.161\u003csup\u003ea\u003c/sup\u003e/0.255\u003csup\u003eb\u003c/sup\u003e/0.437\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eHE4（pmol/L）\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e355.4\u0026plusmn;319.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e89.4\u0026plusmn;69.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e498.9\u0026plusmn;547.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e132.7\u0026plusmn;259.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.039\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e/0.575\u003csup\u003eb\u003c/sup\u003e/0.651\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"118\"\u003e\n\u003cp\u003eCA199（U/ml）\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e248.1\u0026plusmn;525.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e160.6\u0026plusmn;423.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"95\"\u003e\n\u003cp\u003e276.9\u0026plusmn;586.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"103\"\u003e\n\u003cp\u003e220.5\u0026plusmn;547.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"146\"\u003e\n\u003cp\u003e0.556\u003csup\u003ea\u003c/sup\u003e/0.877\u003csup\u003eb\u003c/sup\u003e/0.663\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ea:EOEC\u003cem\u003e vs. \u003c/em\u003eEOCC, b:EOEC \u003cem\u003evs. \u003c/em\u003eOEC, c:EOCC \u003cem\u003evs. \u003c/em\u003eOCC.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparative analysis of pathological characteristics of EAOC and non-EAOC patients(n,%)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-EAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e74\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFIGO stage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.417\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eI/II\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIII/IV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDifferentiation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.932\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMiddle\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHigh\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBiomarker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eER(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.253\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePR(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.094\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP53(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.085\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP16(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.854\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMMR(-)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.114\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKi67(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.8\u0026thinsp;\u0026plusmn;\u0026thinsp;18.94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.767\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNapsin A(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.075\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHNF-1\u0026beta;(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.113\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe rates of ER and PR positivity in the EOEC group were significantly higher than those in the EOCC group (71.4% vs. 17.9%, 60.0% vs. 7.7%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, the rates of HNF-1 and Napsin A positivity in the EOCC group were significantly higher relative to the EOEC group (28.2% vs. 20.0%, 30.8% vs. 7.7%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). HNF-1 and Napsin A positive rates in the OCC group were significantly higher than those in the OEC group (74.2% vs. 16.9%, 80.0% vs. 4.6%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eIntra-group and inter-group pathological characteristics of EAOC and non-EAOC patients(n,%)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEOEC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEOCC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOEC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOCC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e39\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e65\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e35\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFIGO stage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eI/II\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.116\u003csup\u003ea\u003c/sup\u003e/0.767\u003csup\u003eb\u003c/sup\u003e/0.792\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIII/IV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDifferentiation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.177\u003csup\u003ea\u003c/sup\u003e/0.695\u003csup\u003eb\u003c/sup\u003e/0.239\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMiddle\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHigh\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBiomarker\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eER(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.01\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e/0.667\u003csup\u003eb\u003c/sup\u003e/0.311\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePR(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.01\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e/0.880\u003csup\u003eb\u003c/sup\u003e/0.635\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP53(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.526\u003csup\u003ea\u003c/sup\u003e/0.076\u003csup\u003eb\u003c/sup\u003e/0.589\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP16(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.112\u003csup\u003ea\u003c/sup\u003e/0.710\u003csup\u003eb\u003c/sup\u003e/0.912\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMMR(-)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.072\u003csup\u003ea\u003c/sup\u003e/0.548\u003csup\u003eb\u003c/sup\u003e/0.291\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKi67(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.718\u003csup\u003ea\u003c/sup\u003e/0.907\u003csup\u003eb\u003c/sup\u003e/0.564\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNapsin A(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.01\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e/0.459\u003csup\u003eb\u003c/sup\u003e/0.230\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHNF-1\u0026beta;(+)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.01\u003c/strong\u003e\u003csup\u003ea\u003c/sup\u003e/0.317\u003csup\u003eb\u003c/sup\u003e/0.273\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"6\"\u003ea:EOEC \u003cem\u003evs.\u003c/em\u003e EOCC, b:EOEC \u003cem\u003evs.\u003c/em\u003e OEC, c:EOCC \u003cem\u003evs.\u003c/em\u003e OCC.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e(4) Prognostic characteristics\u003c/p\u003e\n\u003cp\u003eOverall, 74 patients in the EAOC group were subjected to initial analyses, 64 of whom were followed up (follow-up rate of 86.5%). Rates of platinum therapy resistance, recurrence and mortality were determined as 6.25%, 39.1%, and 28.1%, respectively. Among the 100 patients in the non-EAOC group, 85 were followed up (85.0%). The platinum resistance rate was determined as 9.41%, recurrence rate as 54.1%, and mortality rate as 40.0%, which were not significantly different between the two groups (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab6\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePrognosis comparison between EAOC and non-EAOC patients(n)\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eEAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003enon-EAOC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e74\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e100\u003c/strong\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ePlatinum resistance\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.483\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eRelapse\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.405\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eDeath\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.193\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eKaplan-Meier analysis and log-rank test showed that the average overall survival (OS) of the EAOC group was 91.6 months (95% CI: 76.9\u0026ndash;106.5 months) while that of the non-EAOC group was 77.8 months (95% CI: 66.1\u0026ndash;90.0 months), with no significant differences (P\u0026thinsp;=\u0026thinsp;0.068, \u0026gt; 0.05). The median progression-free survival (PFS) of the EAOC group was 78.4 months (95% CI: 62.2\u0026ndash;94.5 months), which was not significantly different from the non-EAOC group (64.0 months; 95% CI: 50.7\u0026ndash;77.1 months) (P\u0026thinsp;=\u0026thinsp;0.216, \u0026gt; 0.05), as shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n\u003cp\u003eIntra-group and inter-group analyses of the same pathological types via Kaplan-Meier and log-rank tests showed that OS of the EOCC group was 90.8 months (95% CI, 69.9\u0026ndash;111.8 months), EOEC group was 96.8 months (95% CI, 76.8\u0026ndash;116.8 months), OCC group was 77.4 months (95% CI, 51.49\u0026ndash;103.30 months), and OEC group was 81.10 months (95% CI, 68.0\u0026ndash;94.2 months). We observed no significant differences in OS in EOCC vs. EOEC, EOCC vs. OCC, and EOEC vs. OEC groups (P\u0026thinsp;=\u0026thinsp;0.290, 0.262, 0.070, all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). PFS of patients in the EOCC group was 80.9 months (95% CI, 61.2\u0026ndash;100.6 months), EOEC group was 82.3 months (95% CI 59.4\u0026ndash;105.2 months), OCC group was 85.9 months (95% CI 68.4\u0026ndash;108.3 months), and OEC group was 60.0 months (95% CI 45.50\u0026ndash;74.6 months). We observed no significant differences in PFS in EOCC vs EOEC, EOCC vs OCC, and EOEC vs OEC groups (P\u0026thinsp;=\u0026thinsp;0.222, 0.675, 0.071, all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"4 Discussion","content":" \u003cp\u003eSeveral recent studies have shown that endometriosis patients have significantly increased risk of ovarian cancer[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. As a precancerous lesion, endometriosis is closely related to ovarian clear cell and endometrioid carcinomas. The theory of external origin of ovarian cancer hypothesizes that both clear cell and endometrioid carcinoma of the ovary originate from malignant transformation of endometriosis, which poses a challenge to the current diagnostic criteria for malignant transformation of endometriosis. However, further clinical and basic research evidence is needed to substantiate this theory. In the current study, the two ovarian cancer types(ovarian clear cell carcinoma and ovarian endometrioid carcinoma) most closely associated with endometriosis were examined as a whole. According to the diagnostic criteria of Sampson and Scott, samples were divided into EAOC and non-EAOC groups, and clinicopathologic features and prognosis between the groups compared. Our results showed no significant differences between the groups, supporting the theory that both non-endometriosis-associated primary ovarian endometrial carcinoma and ovarian clear cell carcinoma potentially have the same origin as EAOC from endometriosis.\u003c/p\u003e \u003cp\u003eWe retrospectively analyzed the clinical features of 174 patients from EAOC and non-EAOC groups. The average age and proportion of menopausal patients in the EAOC group was lower than the non-EAOC group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The differences may be attributed to a potential drop in postmenopausal hormone levels, gradual atrophic degradation of ectopic endometrium[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], limitations of pathological materials, and errors due to insufficient pathological evidence of endometriosis, but further experiments on larger sample sizes are required to confirm these findings. No significant differences were evident in BMI, dysmenorrhea history, surgical history, complications, ascites, tumor size and relevant serum tumor markers (CA125, HE4, CA199) between the two groups (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), consistent with earlier results. Our experiments support similar characteristics of endometriosis-associated and non-endometriosis-associated primary ovarian cancers. Furthermore, upon stratified analysis according to pathological type into EOCC and EOEC, OCC and OEC groups, relevant epidemiological and clinical characteristics, such as BMI, dysmenorrhea history, history of surgery, complications, ascites, tumor size and serum tumor marker (CA125, HE4, CA199) levels were not significantly different (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Our findings provide further evidence that primary ovarian endometrial carcinoma and clear cell carcinoma are associated with corresponding pathological types in endometriosis-associated ovarian cancer, with similar clinical features.\u003c/p\u003e \u003cp\u003eHistopathology evaluation is the gold standard of ovarian cancer diagnosis and classification. Immunohistochemical analysis revealed high expression of ER and PR in endometrioid carcinoma of ovary and low expression in clear cell carcinoma[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Compared with other epithelial ovarian cancer types, the characteristics of ovarian clear cell carcinoma included HNF-1β increase, high expression of Napsin A and positive expression of P53[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. MMR expression in ovarian endometrial carcinoma and clear cell carcinoma is abnormally higher than that in other subtypes of ovarian cancer[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The above molecules are therefore useful as biomarkers to distinguish epithelial ovarian cancer subtypes. Ki-67 is currently used as a positive nuclear proliferation marker and its expression reflects the biological behavior of tumor cells[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. For analysis of differences, similarities and potential mechanisms of EAOC and non-EAOC, we compared the pathologies of the two groups. Our data showed no histological differences in terms of pathologic differentiation degree, ER, PR, P53, and P16, Ki67, MMR, HNF-1β and Napsin A-positive expression (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) between EAOC and non-EAOC groups.The majority of previous reports have focused on the malignant transformation of endometriosis and few studies have been conducted on the characteristics of different pathological types of endometrial carcinoma and clear cell carcinoma. However, there are a number of specific differences in clinicopathological characteristics between endometrioid and clear cell carcinoma types. Further grouping analysis revealed no significant differences in expression of relevant non-specific indicators, such as P53, P16, Ki67 and MMR, among the groups. The positive expression rates of ER and PR were markedly different between endometrioid carcinoma and clear cell carcinoma groups, but not from the primary ovarian carcinoma of the same pathologic type. Differentiation of endometriosis into two tissue types is reported to occur in a dual mode regulated by sex hormones [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]: (1) estrogen and progesterone receptor-positive endometriosis lesions undergo malignant transformation to form hormone-dependent endometrioid carcinoma after long-term stimulation without antagonistic estrogen and (2) atrophic ectopic endometrial lesions negative for estrogen and progesterone receptors are stimulated by oxidative stress for a long period of time, resulting in malignant transformation and formation of non-hormone-dependent clear cell carcinoma. The results of this study were consistent with earlier literature, validating that clear cell carcinoma is a non-hormone-dependent tumor. The positive expression rates for HNF-1β and Napsin A were significantly higher in the clear cell carcinoma than endometrioid carcinoma group. Accordingly, we conclude that different histological types undergo distinct mechanisms for development of endometriosis-associated ovarian cancer, which will be the focus of follow-up investigations.\u003c/p\u003e \u003cp\u003eThe majority of previous studies focused on comparing clinicopathological and prognostic differences between intrauterine endometriosis-associated ovarian cancers of a single pathologic type. However, sample sizes were usually small and the results obtained were inconsistent. Some findings suggest that ovarian endometrial carcinoma and ovarian clear cell carcinoma are early phases with better prognosis than the two pathological types of primary ovarian cancer[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], while other researchers have reported no obvious differences[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Here, we examined 174 cases of ovarian endometrial carcinoma and clear cell carcinoma, with a median follow-up period of 67 months. Our data showed that platinum resistance, recurrence and mortality rates between the EAOC and non-EAOC groups were not significantly different (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). PFS and OS were comparable between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), supporting similar prognosis of EAOC and non-EAOC. In 2020, Marjolein Hermens [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] analyzed 32,419 patients with ovarian cancer and found synchronous endometriosis of ovarian cancer staging of early, higher survival and overall survival is longer, perhaps because of more frequent hospital visits of patients with endometriosis due to simultaneous treatment with endometriosis drugs, long-term state of inflammation caused by endometriosis, which activates immune function, in turn, leading to early detection and better prognosis, giving rise to the theory that ovarian cancer with endometriosis may have different pathophysiological features to other ovarian cancer types.Earlier studies have established a low early incidence of epithelial ovarian cancer. In this research, early incidence rates of EAOC and non-EAOC were 68.9% and 63.0%, respectively, which were significantly higher than the average early incidence of ovarian cancer (30.0%). Overall survival rates of the EAOC and non-EAOC groups were 71.9% and 60.0%, which were significantly higher than the average five-year survival rate of ovarian epithelial carcinoma (44%- 50%)[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Further indicates that ovarian clear cell carcinoma and endometrioid carcinoma are sources of malignant transformation of endometriosis, therefore can be detected early. But accelerated growth of tumor tissue destroys the tissue of origin because of malignant transformation,pathological materials can not remove cancer and ectopic foci lesions at the same time, consequently, a proportion of clear cell and endometrioid carcinomas of the ovary are not diagnosed as endometriosis-associated ovarian cancer.\u003c/p\u003e \u003cp\u003eIn summary, no obvious clinicopathological differences between EAOC and non-EAOC were observed in this study, leading to the speculation that primary ovarian endometrial and clear cell carcinoma have the same origin with EAOC. Our findings support the theory of dualism of ovarian cancer that endometrial carcinoma and clear cell carcinoma originate from progression of ovarian endometriosis. Therefore, it is worth exploring whether the stringent diagnostic criteria for malignant transformation of endometriosis require revision. However, the retrospective nature of this study is a limitation, and further large-scale, prospective multicenter clinical and molecular biology studies are required to verify the associations of malignant transformation of endometriosis with ovarian clear cell and endometrial carcinomas, which should aid in clarifying the biological mechanisms and developing individualized treatments for patients with endometriosis-associated ovarian cancer.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEAOC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eendometriosis-associated ovarian cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003enon-EAOC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-endometriosis-associated primary ovarian cancer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEOCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eendometriosis associated ovarian clear cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEOEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eendometriosis associated ovarian endometrioid carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eclear cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOEC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eendometrioid carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody Mass Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eoverall survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePFS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprogression-free survival\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eSamples were fully encoded to protect patient confidentially. The study and its protocols were approved by the Research Ethics committees of Liaoning Cancer Hospital \u0026amp; Institute (2020G0322).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by grants from The National Natural Science Foundation of China, Grant Number:81771556.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eHW\u0026nbsp;and CC carried out most parts of the experiment; YZ\u0026nbsp;participated in the experiment; DW participated in the design of the study;\u0026nbsp;HW, CC and\u0026nbsp;PC\u0026nbsp;performed the statistical analysis. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGiudice LC. Endometriosis. N Engl J Med. 2010;362:2389\u0026ndash;98. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMcp1000274\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErzen M, Rakar S, Klancnik B, Syrj\u0026auml;nen K. Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol. 2001;83:100\u0026ndash;8. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1006/gyno.2001.6382\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSampson J. Endometrial carcinoma of the ovary arising in endo metrial tissue in that organ. Arch Surg. 1925;10:1\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScott R. Malignant change in endometriosis. Obstet Gynecol. 1953;2:293\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSwiersz LM. Role of endometriosis in cancer and tumor development. Ann NY Acad Sci. 2002;955:281\u0026ndash;92. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1749-6632.2002.tb02788.x\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGadducci A, Lanfredini N, Tana R. Novel insights on the malignant transformation of endometriosis into ovarian carcinoma. Gynecol Endocrino. 2014;30:612\u0026ndash;7. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/09513590.2014.926325\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVercellini P, Vigan\u0026ograve; P, Buggio L, Makieva S, Scarfone G, Cribi\u0026ugrave; FM, Parazzini F, Somigliana E. Perimenopausal management of ovarian endometriosis and associated cancer risk:When is medical or surgical treatment indicated?Best practice and research. Clin Obstetri Gynaecol. 2018;51:151\u0026ndash;68. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bpobgyn.2018.01.017\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBas-Esteve E, P\u0026eacute;rez-Arguedas M, Guarda-Muratori GA, Aci\u0026eacute;n M, Aci\u0026eacute;n P. Endometriosis\u0026ensp;and\u0026ensp;ovarian\u0026ensp;cancer:Their association and relationship.Eur J Obstet Gynecol Reprod Biol X. 3(2019)100053. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eurox.2019.100053\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMallen A, Soong TR, Townsend MK, Wenham RM, Crum CP, Tworoger SS. Surgical prevention strategies in ovarian cancer. Gynecol Oncol. 2018;151:166\u0026ndash;75. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ygyno.2018.08.005\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRen F, Wang D, Jiang Y. Fengyan Ren.Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis.Arch Gynecol Obstet. 285(2012)215\u0026ndash;221. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00404-011-1922-x\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo C, Ren F, Wang D, Li Y, Liu K, Liu S, Chen P. RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis. Oncology Reports. 2014;32:2580\u0026ndash;8. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3892/or.2014.3524\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEleftherios P, Samartzis SI, Labidi-Galy M, Moschetta M, Uccello, Dimitrios R, Kalaitzopoulos JA, Perez-Fidalgo. Stergios Boussios. Endometriosis-associated\u0026ensp;ovarian\u0026ensp;carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review. Ann Transl Med. 2020;8:1712. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21037/atm-20-3022a\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang S, Qiu L, Lang JH, Shen K, Yang JX, Huang HF, Pan LY, Wu M. Clinical analysis of ovarian epithelial carcinoma with coexisting pelvic endometriosis. Am J Obstet Gynecol. 2013;208:411\u0026ndash;5. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajog.2012.12.004\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen S, Dai X, Gao Y, Shen F, Ding J. Qi Chen.The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer.Sci Rep. 7(2017) 16922. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41598-017-17265-6\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhilip PC, Ip S-Y, Wang, Oscar GW, Wong K-L, Chow HHok-Yeung, Lee, Annie NY, Cheung K-Y. Tse. Napsin A, Hepatocyte Nuclear Factor-1-Beta (HNF-1β), Estrogen and Progesterone Receptors Expression in Arias-Stella Reaction. Am J Surg Pathol. 2019;43:325\u0026ndash;33. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PAS.0000000000001212\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJennifer A, Bennett V, Morales-Oyarvide S, Campbell TA, Longacre EO. Mismatch Repair Protein Expression in Clear Cell Carcinoma of the Ovary: Incidence and Morphologic Associations in 109 Cases. Am J Surg Pathol. 2016;40:656\u0026ndash;63. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/PAS.0000000000000602\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMunjishvili V, Barabadze E, Musashvili T, Gachechiladze M, Burkadze G. Morphophenotypic Characteristics of Ovarian Serous Borderline Tumors. Georgian Med News. 2019;290:20\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFumihiko Suzuki J-I, Akahira I, Miura T, Suzuki K, Ito S-I, Hayashi H, Sasano N, Yaegashi. Loss of estrogen receptor beta isoform expression and its correlation with aberrant DNA methylation of the 5\u0026rsquo;-untranslated region in human epithelial ovarian carcinoma. Cancer Sci. 2008;99:2365\u0026ndash;72. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1349-7006.2008.00988.x\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanase Y, Yamada Y, Shigetomi H, Kajihara H, Oonogi A, Yoshizawa Y, Furukawa N, Haruta S, Yoshida S, Sado T, Oi H, Kobayashi H. Modulation of estrogenic action in clear cell carcinoma of the ovary. Exp Ther Med. 2012;3:18\u0026ndash;24. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3892/etm.2011.376\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRen T, Wang S, Sun J, Qu JM, Xiang Y, Shen K, Lang JH. Endometriosis\u0026ensp;is the independent prognostic factor for survival in Chinese patients with epithelial ovarian\u0026ensp; carcinoma. J Ovarian Res. 2017;10:67. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13048-017-0363-y\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark JY, Kim DY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH. Significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma. Int J Gynecol Cancer. 2018;28:11\u0026ndash;8. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/IGC.0000000000001136\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Q, Sun Y, Zhang X, Wang L, Wu W, Wu M, Meng C, Liu G. Endometriosis-associated ovarian cancer is a single entity with distinct clinicopathological characteristics. Cancer Biol Ther. 2019;20:1029\u0026ndash;34. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/15384047.2019.1595278\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao T, Shao Yu, Liu Y, Wang X, Guan L, Lu Y. Endometriosis\u0026ensp;does not confer improved prognosis in\u0026ensp;ovarian\u0026ensp;clear cell\u0026ensp;carcinoma: a retrospective study at a single institute. J Ovarian Res. 2018;11:53. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13048-018-0425-9\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarjolein Hermens, Anne M, van Altena M, van der Aa J, Bulten, Huib AAM, van Vliet AG, Siebers, Ruud LM, Bekkers. Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women. Am J Obstet Gynecol. 2021;224:284.e1-284.e10. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ajog.2020.08.056\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoufarrij S, Dandapani M, Arthofer E, Gomez S, Srivastava A, Lopez-Acevedo M, Villagra A, Chiappinelli KB. Epigenetic therapy for ovarian cancer: promise and progress.Clin Epigenetics.11(2019):7. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13148-018-0602-0\u003c/span\u003e\u003c/span\u003e.\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":"endometriosis-associated ovarian cancer, ovarian clear cell carcinoma, ovarian endometrioid carcinoma, diagnostic criteria","lastPublishedDoi":"10.21203/rs.3.rs-651274/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-651274/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: To establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis.\u003c/p\u003e\u003cp\u003eMethods: Retrospectively collected clinicopathological and follow-up data of 174 clear cell and endometrial ovarian cancer patients. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer, and comparative analysis of the clinicopathological characteristics and prognosis conducted.\u003c/p\u003e\u003cp\u003eResults: Average age and proportion of menopausal patients in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P\u0026lt;0.05). Other clinicopathological features examined, including body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA199, stage,\u0026nbsp;differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1β and Napsin A were not significantly different between the groups (P\u0026gt;0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P \u0026gt; 0.05).\u003c/p\u003e\u003cp\u003eConclusion: Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Correlation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary Ovarian Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-06-28 18:24:10","doi":"10.21203/rs.3.rs-651274/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":"12e7e0e6-704f-4627-808a-fdb0f0194ab6","owner":[],"postedDate":"June 28th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":5320831,"name":"Surgery"},{"id":5320832,"name":"Oncology"}],"tags":[],"updatedAt":"2021-10-08T21:49:08+00:00","versionOfRecord":[],"versionCreatedAt":"2021-06-28 18:24:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-651274","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-651274","identity":"rs-651274","version":["v1"]},"buildId":"2u56kwukJI3zHK-uzyFNs","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}