Synchronous TP53-Aberrant Ovarian and Cervical Carcinomas in a Patient with Parkinson’s Disease: Molecular Insights and Clinical Challenges

Synchronous TP53-Aberrant Ovarian and Cervical Carcinomas in a Patient with Parkinson’s Disease: Molecular Insights and Clinical Challenges | 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 Case Report Synchronous TP53-Aberrant Ovarian and Cervical Carcinomas in a Patient with Parkinson’s Disease: Molecular Insights and Clinical Challenges Chenhui Wang, Shan Pan, Weigen Zhou, Kang Wu, Jianqing Zhou, Anwen Wei, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8913489/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background The synchronous occurrence of bilateral ovarian high-grade serous carcinoma (HGSC) and primary gastric-type endocervical adenocarcinoma (GEA) is exceedingly rare, with limited understanding of their molecular relationship and clinical management. This report presents a unique case of dual primary gynecologic malignancies in a patient with Parkinson’s disease, highlighting diagnostic challenges, therapeutic complexities, and potential shared oncogenic pathways. Case Presentation: A 67-year-old female with a 6-year history of Parkinson’s disease presented with lower abdominal distension, pain, and altered bowel habits. Imaging revealed bilateral adnexal masses with local invasion. Surgical resection confirmed synchronous bilateral HGSC (FIGO stage III) and GEA (superficial myometrial invasion), both exhibiting aberrant p53 expression (heterogeneous pattern), high Ki-67 (∼80%), and mismatch repair proficiency. Immunohistochemical profiling suggested involvement of the BRCA/TP53 pathway. Conclusion This case underscores the rarity of synchronous HGSC and GEA, both demonstrating TP53 dysfunction, potentially indicating a common molecular etiology. Comprehensive genetic testing (e.g., BRCA1/2, TP53) is critical to elucidate clonality and guide targeted therapy. The presence of Parkinson’s disease further complicates management, emphasizing the need for personalized, multimodal treatment strategies. This report advocates for heightened clinical suspicion of synchronous malignancies in patients with persistent pelvic symptoms and supports integrated molecular profiling to optimize therapeutic outcomes. Ovarian high-grade serous carcinoma Gastric-type endocervical adenocarcinoma PARP inhibitors Case report Figures Figure 1 Figure 2 1. Introduction Ovarian high-grade serous carcinoma (HGSC) is the most common and lethal histological subtype of epithelial ovarian cancer, accounting for approximately 70% of ovarian cancer deaths [ 1 ] The majority of HGSCs are now believed to originate from the fallopian tube epithelium [ 2 ] , characterized nearly universally by TP53 mutations and frequently associated with homologous recombination deficiency (HRD), particularly in carriers of BRCA1 or BRCA2 pathogenic variants [ 3 ] . This molecular profile has profound therapeutic implications, notably sensitivity to platinum-based chemotherapy and PARP inhibitors [ 4 ] . Concurrently, primary gastric-type endocervical adenocarcinoma (GEA) represents a rare, aggressive variant, accounting for less than 10% of all cervical adenocarcinomas [ 5 , 6 ] . It is notably unrelated to high-risk human papillomavirus (HPV) infection and is instead associated with mutations in STK11, ERBB2, and occasionally TP53, exhibiting a distinct clinical behavior characterized by late recurrence and poor response to conventional therapies [ 7 – 10 ] . The synchronous occurrence of dual primary gynecologic malignancies, particularly HGSC and GEA, is exceptionally rare. Current literature is sparse, primarily limited to isolated case reports, and the molecular relationship between these two distinct entities remains largely unexplored. A critical unanswered question is whether their co-occurrence is a stochastic event or suggests an underlying shared oncogenic pathway, such as a common germline or somatic predisposition involving TP53 or other DNA damage response genes. Furthermore, the clinical management of such complex cases is not standardized, posing significant challenges in staging, treatment prioritization, and long-term surveillance. This case report delineates the unique clinical, pathological, and molecular features of a 67-year-old woman with a 6-year history of Parkinson’s disease who presented with synchronous bilateral ovarian HGSC and a primary gastric-type endocervical adenocarcinoma. Comprehensive immunohistochemical profiling revealed aberrant p53 expression (heterogeneous pattern) and a high proliferative index (Ki-67 ~ 80%) in both neoplasms, strongly suggestive of concurrent TP53 mutagenesis and a potential common oncogenic driver, possibly within the BRCA/TP53 axis. This molecular convergence in two morphologically and anatomically distinct tumors presents a compelling argument for a shared genetic etiology rather than a mere coincidence. The presence of significant comorbidities, namely Parkinson’s disease, introduces an additional layer of complexity to the perioperative and systemic management of this elderly patient, influencing decisions regarding chemotherapy tolerance, potential drug interactions with levodopa, and overall functional reserve. Therefore, this case serves two primary purposes: First, it provides a detailed clinicopathological description of a highly unusual dual malignancy, enriching the limited literature on such synchronous presentations. Second, it proposes a hypothesis of a unified molecular pathogenesis, underscoring the critical role of comprehensive genetic testing (including BRCA1/2 and TP53) in explaining carcinogenesis and guiding targeted therapeutic strategies. By highlighting the diagnostic challenges, therapeutic dilemmas, and molecular insights, this report aims to contribute to the understanding of rare tumor associations and advocate for personalized, genotype-driven management in complex oncological scenarios. 2. Presentation of case A 67-year-old female with a 6-year history of Parkinson’s disease, maintained on levodopa–benserazide (0.125 g orally three times daily), presented with a 6-month history of lower abdominal distension and altered bowel habits, followed by 15 days of persistent dull lower abdominal pain accompanied by bloating and difficulty defecating. She was admitted for further evaluation. Laboratory investigations revealed significantly elevated tumor markers: HE4 932.70 pmol/L, CA-125 1579.09 U/mL, and CA-153 366.70 U/mL. Imaging studies, including abdominal CT and pelvic MRI, identified large bilateral adnexal complex cystic-solid masses (left: 75×137×65 mm; right: 107×137×161 mm), highly suggestive of malignancy with involvement of the uterus, sigmoid colon, and rectum. A chest CT revealed a small nodule in the right upper lobe. Colonoscopy showed colonic polyps, and gastroscopy indicated chronic active atrophic gastritis (C-1). Cervical screening (HPV and TCT) was negative. The patient underwent exploratory laparotomy in February 2025, which revealed approximately 50 mL of ascitic fluid, bilateral enlarged ovaries adherent to surrounding structures, and miliary nodules on the omentum. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and adhesiolysis. Final pathology confirmed: 1. Bilateral high-grade serous ovarian carcinoma with lymphovascular invasion and involvement of the left fallopian tube, appendix, and omentum; 2. Primary gastric-type endocervical adenocarcinoma (non-HPV related), with superficial myometrial invasion; 3. Concurrent benign findings including uterine adenomatoid tumor, leiomyoma with calcification, and endometrial polyp. Immunohistochemical profiling supported a BRCA/p53-related pathway abnormality, with heterogeneous p53 expression, high Ki-67 (80%+), and mismatch repair proficiency. The patient is currently recovering postoperatively, with plans for genetic testing and adjuvant therapy. In summary, the entire clinical course of this case—from symptom onset, through imaging and laboratory investigations, surgical intervention, to postoperative pathological assessment and treatment planning—can be outlined in the following timeline(Fig. 1 ). 3. Discussion This report presents a diagnostically and therapeut complex case of a 67-year-old female with Parkinson’s disease who was diagnosed with synchronous primary malignancies: bilateral high-grade serous ovarian carcinoma (HGSC) and gastric-type endocervical adenocarcinoma (GEA). The patient exhibited markedly elevated tumor markers and radiographic signs of local invasion. She underwent comprehensive surgical resection, with pathological examination confirming advanced HGSC with transcoelomic dissemination and a concurrent HPV-independent cervical adenocarcinoma showing superficial invasion. This case is particularly notable due to the exceptionally rare co-occurrence of two histologically and etiologically distinct gynecologic malignancies, both demonstrating immunohistochemical evidence of TP53 dysfunction, in a patient with a pre-existing neurodegenerative disorder. This unusual presentation raises compelling questions regarding potential shared oncogenic pathways, such as BRCA/TP53 aberrations, and underscores the salient challenges in geriatric oncology care for patients with significant comorbidities. Consequently, this case provides valuable clinical insights and serves as an instructive example regarding multimodal diagnostics, the role of genetic profiling in elucidating cancer etiology, and the complexities of treatment planning in the context of concurrent chronic illness. The patient initially presented with lower abdominal pressure and pain. Imaging, histopathological, and immunohistochemical analyses confirmed synchronous bilateral ovarian HGSC and cervical GEA, representing a rare instance of dual primary malignancy. Ovarian HGSC, the most common and aggressive form of epithelial ovarian cancer, is frequently associated with TP53 mutations and BRCA pathway abnormalities [ 1 ] . In this case, the bilateral ovarian tumors were large, with invasion into adjacent structures, ascites, and omental metastasis, consistent with typical HGSC behavior. Simultaneously, the patient was diagnosed with cervical GEA, a rare HPV-independent adenocarcinoma accounting for approximately 10%–15% of all cervical adenocarcinomas. This tumor type exhibits morphological and immunophenotypic characteristics—such as MUC6 and HIK1083 positivity—resembling gastric epithelium [ 11 ] . GEA is generally aggressive, carries a poor prognosis, and occurs more frequently in older women [ 9 ] . Notably, both malignancies showed aberrant p53 expression, a high Ki-67 proliferation index (approximately 80%), and discordant ER/PR receptor status, suggesting possible common oncogenic mechanisms. Immunohistochemical analysis revealed retained expression of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2), effectively excluding Lynch syndrome and further supporting a potential role for BRCA1/2 or TP53 mutations in tumor development [ 12 ] . Although ovarian high-grade serosa carcinoma (HGSC) and GEA originate from distinct histological lineages, the shared observation of aberrant p53 expression implies that TP53 mutation may contribute significantly to their synchronous occurrence. Moreover, although BRCA mutations are frequently identified in HGSC, they have also been reported in certain cases of GEA [ 13 , 14 ] . The immunohistochemical profile in this patient suggests that both malignancies may involve dysregulation within the BRCA/TP53 pathway. Further investigation utilizing next-generation sequencing (NGS) to assess the mutation status of BRCA1/2 and TP53 is warranted to elucidate whether these tumors are clonally related—derived from a common progenitor cell—or represent independent primary malignancies. The identification of identical pathogenic mutations in both tumors would support a clonal origin, whereas divergent genetic profiles would indicate independent tumorigenesis. This distinction bears substantial clinical relevance, as clonally related tumors may exhibit susceptibility to PARP inhibitors, while independently arising tumors would necessitate tailored therapeutic approaches [ 15 , 16 ] . The patient initially reported six months of “discomfort and a sensation of pressure in the lower abdomen,” accompanied by changes in bowel habits. These symptoms progressed to persistent lower abdominal pain and distension. Such nonspecific manifestations can easily mimic benign pelvic conditions—such as ovarian cysts, uterine fibroids, or pelvic inflammatory disease—or functional gastrointestinal disorders [ 17 ] . In elderly patients especially, gastrointestinal symptoms are often attributed to age-related functional changes or common entities like constipation or irritable bowel syndrome, frequently resulting delayed diagnosis of malignancy [ 18 ] . This case underscores the importance of considering occult gynecologic malignancies—including ovarian cancer and non-HPV-associated cervical adenocarcinomas—in cases of persistent pelvic discomfort accompanied by bowel habit changes, even when initial evaluations are unremarkable. Abdominal-pelvic CT and MRI were instrumental in the initial assessment of tumor extent, local invasion, and lymph node involvement. CT imaging demonstrated large, complex cystic-solid pelvic masses bilaterally with invasion into adjacent structures. MRI provided superior delineation of anatomical relationships with adjacent organs such as the sigmoid colon, rectum, and posterior uterine wall, while also revealing features suggestive of malignancy, including restricted diffusion and prominent contrast enhancement [ 19 ] . Nevertheless, although imaging findings were highly indicative of malignancy, they lacked the specificity required to differentiate between synchronous primary carcinomas and metastatic spread, or to determine the exact histological subtype [ 20 ] . Definitive diagnosis remains dependent on thorough histopathological and immunohistochemical evaluation. These imaging and immunohistochemical features are shown in Fig. 2 . Panel A shows the complex cystic-solid masses in the bilateral adnexal regions seen on pelvic MRI and CT, with invasion into adjacent structures. Panel B displays the corresponding histopathological sections (hematoxylin and eosin [H&E] staining) for the cervical gastric-type adenocarcinoma and the ovarian high-grade serous carcinoma, alongside the expression profiles of key immunohistochemical markers (p53, Ki-67, p16, estrogen receptor [ER], progesterone receptor [PR], HER2, and mismatch repair proteins). GEA is a rare but highly aggressive subtype of cervical cancer that is not associated with human papillomavirus (HPV) infection. It occurs predominantly in elderly women and often presents with non-specific symptoms, frequently leading to oversight or misdiagnosis [ 20 ] . In the present case, the patient’s cervical screening—including HPV testing and cytology—yielded unremarkable results; nevertheless, she was postoperatively diagnosed with GEA based on histopathological findings. This underscores that even with normal cervical morphology and cytology, the possibility of a non-HPV-associated adenocarcinoma cannot be ruled out. Additionally, the patient was diagnosed with a concurrent ovarian high-grade serous carcinoma (HGSC). Although these two malignancies may share molecular alterations such as TP53 or BRCA mutations, a careful distinction must be made between synchronous primary carcinomas and metastatic disease [ 21 ] . Such cases highlight the importance of maintaining a broad differential diagnosis when evaluating complex pelvic masses. A comprehensive diagnostic approach incorporating imaging, tumor marker assays, and intraoperative frozen section analysis is essential. When warranted, immunohistochemical staining and molecular profiling should be promptly employed to establish a definitive diagnosis. For advanced epithelial ovarian cancer, primary debulking surgery (PDS) represents a cornerstone of treatment with the goal of achieving long-term survival. Intraoperative assessment in this case revealed extensive pelvic and abdominal disease, including omental metastasis, but no evidence of distant lymph node or parenchymal organ involvement. The patient therefore underwent comprehensive cytoreductive surgery, comprising total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and lysis of intestinal adhesions. Although complete macroscopic resection (R0) was not attained due to suspected residual disease on intestinal surfaces, maximal effort toward optimal (R1) cytoreduction is a critical prognostic factor [ 22 ] . Notably, the patient also had a concurrent diagnosis of GEA—a tumor type generally resistant to radiotherapy and conventional chemotherapy, for which surgical resection remains the primary treatment [ 9 ] . Thus, the extensive surgical intervention was appropriate for addressing both the ovarian carcinoma and the synchronous cervical GEA. Postoperative adjuvant therapy should be tailored according to the final FIGO staging. Ovarian high-grade serous carcinoma (HGSC) is typically sensitive to platinum-based agents, with carboplatin plus paclitaxel constituting first-line adjuvant chemotherapy [ 23 ] . Immunohistochemical results showing aberrant p53 expression and a high Ki-67 proliferation index suggest an underlying TP53 mutation. Further genetic evaluation for BRCA1/2 mutations and homologous recombination deficiency (HRD) status is recommended to assess potential susceptibility to poly-ADP ribose polymerase (PARP) inhibitors. Should a BRCA mutation or HRD be confirmed, maintenance therapy with a PARP inhibitor such as olaparib may be indicated, as this approach has been shown to significantly prolong progression-free survival. In contrast, GEA generally exhibits poor response to conventional chemoradiation, necessitating a more individualized therapeutic strategy. In this case, HER2 (ErbB-2) immunohistochemistry was scored 1+. If fluorescence in situ hybridization (FISH) confirms HER2 amplification, targeted therapy with anti-HER2 agents such as trastuzumab could be considered. Moreover, GEA is frequently associated with mutations in genes such as STK11 and KRAS. Comprehensive genomic profiling via next-generation sequencing (NGS) is therefore advised to identify additional potential therapeutic targets, including alterations amenable to targeted agents such as mTOR inhibitors [ 5 ] . The prognosis of synchronous primary malignancies is influenced by multiple factors, including tumor stage, histological type, molecular characteristics, and the patient’s performance status [ 24 ] . In this case, the ovarian cancer involved the omentum, appendix, and fallopian tubes, with lymphovascular space invasion indicating a FIGO stage of at least III, which is associated with an unfavorable prognosis. Although the cervical gastric-type adenocarcinoma was limited to the superficial myometrium, it exhibits more aggressive biological behavior than conventional cervical adenocarcinoma and is associated with a propensity for late recurrence [ 25 ] . Immunohistochemical analysis demonstrated aberrant p53 expression, a high Ki-67 proliferation index (approximately 80%), and discordant estrogen receptor (ER) and progesterone receptor (PR) expression. These features are consistent with high-grade serous carcinoma and suggest possible TP53 and BRCA1/2 mutations [ 26 ] . Although such tumors are generally sensitive to platinum-based chemotherapy, they carry a high risk of recurrence. Genetic counseling and testing are therefore advised to assess eligibility for PARP inhibitor therapy. Additionally, the tumor exhibited retained/positive expression of all mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6), effectively excluding Lynch syndrome. Nonetheless, other genetic susceptibility factors should still be investigated. A primary limitation is the single-case design. Although the patient received comprehensive preoperative evaluation, successful surgical treatment, and detailed postoperative histopathological and immunohistochemical assessment, the findings and conclusions drawn from a single case have inherently limited generalizability. Whether common patterns exist in the pathogenesis, clinical behavior, and treatment responses of synchronous primary malignancies requires validation through larger clinical studies. Moreover, the patient’s comorbid Parkinson’s disease likely affected her treatment tolerance and prognosis, a factor that may not be common among other patients. This case also highlights promising avenues for further investigation. The two malignancies may share alterations in molecular pathways such as BRCA/p53. Although this hypothesis is supported by immunohistochemical results—including aberrant p53 expression and a high Ki-67 index—it lacks confirmation through direct genetic sequencing. Therefore, we recommend future large-scale, multi-center cohort studies of synchronous primary gynecological cancers incorporating systematic next-generation sequencing (e.g., whole-exome sequencing). Such research is crucial for elucidating common oncogenic drivers, clonal evolutionary relationships, and tumor microenvironment features. This approach would help clarify whether these tumors are clonally related or independent, and could inform the development of precision treatments targeting shared pathways, such as PARP inhibitor therapy. Finally, genetic testing results for this case are still pending, constituting a notable limitation but also suggesting a clear avenue for subsequent investigation. Once germline and somatic mutation statuses of BRCA1/2 and TP53 are confirmed, future analyses should focus on correlating these genetic alterations with the patient’s response to platinum-based chemotherapy, targeted agents, progression-free survival (PFS), and overall survival (OS). Such correlation will help validate current hypotheses regarding molecular subtype-guided therapy and contribute to the development of more individualized prognostic models and treatment strategies for this patient population. In summary, this case underscores the importance of maintaining a high index of suspicion for both HPV-independent cervical carcinomas and synchronous primary malignancies. Despite its limitations, it offers a useful framework for future mechanistic research and clinical decision-making. We encourage collaborative efforts within the research community to improve outcomes for patients with such rare and complex gynecologic tumors through the accumulation of larger case series, prospective molecular profiling, and the establishment of comprehensive clinical databases with long-term follow-up. 4. Conclusion This rare case of synchronous TP53-aberrant HGSC and GEA suggests a potential common oncogenic driver, warranting comprehensive genetic profiling (e.g., BRCA1/2, TP53) to clarify clonality and guide targeted therapy. The coexistence of Parkinson’s disease further underscores the need for individualized treatment strategies. We advocate for integrated molecular diagnostics in patients with atypical pelvic presentations to optimize management of such complex malignancies. Abbreviations HGSC High-grade Serous Carcinoma GEA Gastric-type Endocervical Adenocarcinoma HRD Homologous Recombination Deficiency HPV Human Papillomavirus CT Computed Tomography MRI Magnetic Resonance Imaging BRCA Breast cancer gene ER Estrogen Receptor PR Progesterone Receptor PDS Primary Debulking Surgery PARP Poly-ADP Ribose Polymerase NGS Next-generation Sequencing MMR Mismatch Mepair PFS Progression-free Survival OS Overall Survival Declarations Acknowledgements Not applicable. Authors ’ contributions C.W. conceptualized the study, collected clinical data, and wrote the original draft. S.P. coordinated the project and reviewed the manuscript. K.W. and A.W. assisted in clinical data collection and analysis. J.Z. and Q.C. performed data analysis and interpretation. W.Z. conducted pathological examinations and provided all pathological images.Y.Z. and Y.S. contributed to literature review and data curation. Y.S. supervised the research, revised the manuscript critically, and acted as corresponding author. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Clinical trial number Not applicable. Data availability The datasets used during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Not applicable. Consent for publication This case report and its accompanying images were published with the written informed consent of the patient's relative. The consent form is available for review by the Editor-in-Chief upon request. Competing interests The authors declare no competing interests. References null. Integrated genomic analyses of ovarian carcinoma[J]. 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ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease[J]. Int J Gynecol Cancer, 2019,29(4):728–760. 10.1136/ijgc-2019-000308 Skelton WP, Ali A, Skelton MN, et al. Analysis of Overall Survival in Patients With Multiple Primary Malignancies: A Single-center Experience[J]. Cureus. 2019;11(4):e4552. 10.7759/cureus.4552 . You X, He L, Lin Y, et al. Case Report: A rare case of gastric-type adenocarcinoma of stumps of duplicated cervices in a 49-year-old woman: A case with hidden focus confused us a lot[J]. Front Oncol. 2023;13:1109731. 10.3389/fonc.2023.1109731 . Kanno K, Nakayama K, Razia S, et al. Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor[J]. Curr Issues Mol Biol. 2024;46(9):9376–85. 10.3390/cimb46090555 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 Apr, 2026 Reviewers agreed at journal 27 Mar, 2026 Reviewers invited by journal 17 Mar, 2026 Editor assigned by journal 16 Mar, 2026 Editor invited by journal 23 Feb, 2026 Submission checks completed at journal 21 Feb, 2026 First submitted to journal 21 Feb, 2026 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-8913489","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":607676937,"identity":"e9b791aa-45d0-47d8-bcae-861897550049","order_by":0,"name":"Chenhui Wang","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Chenhui","middleName":"","lastName":"Wang","suffix":""},{"id":607676938,"identity":"5b4f4f9f-36f1-4773-8ce7-0b42559fb876","order_by":1,"name":"Shan Pan","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Shan","middleName":"","lastName":"Pan","suffix":""},{"id":607676939,"identity":"dc39bddf-f80d-45a2-bfba-a5307a872d86","order_by":2,"name":"Weigen Zhou","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Weigen","middleName":"","lastName":"Zhou","suffix":""},{"id":607676940,"identity":"001bb24a-2372-4199-b5e1-0c2a44fcec4b","order_by":3,"name":"Kang Wu","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Kang","middleName":"","lastName":"Wu","suffix":""},{"id":607676941,"identity":"b8a2abce-bb0a-45fd-9b7d-3244ced99288","order_by":4,"name":"Jianqing Zhou","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Jianqing","middleName":"","lastName":"Zhou","suffix":""},{"id":607676942,"identity":"437cb459-26eb-4555-941f-b94b270fa48b","order_by":5,"name":"Anwen Wei","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Anwen","middleName":"","lastName":"Wei","suffix":""},{"id":607676943,"identity":"e7df7b10-af1c-4dee-b552-4cdba5e13fa5","order_by":6,"name":"Qiang Chen","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Chen","suffix":""},{"id":607676944,"identity":"5471a904-6276-4f08-a110-39e24ef8cf3b","order_by":7,"name":"Yifeng Shao","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Yifeng","middleName":"","lastName":"Shao","suffix":""},{"id":607676945,"identity":"6dffeb9d-91c9-4aa6-86ab-f88ab53f644e","order_by":8,"name":"Yingjie Zhu","email":"","orcid":"","institution":"Jiaxing University","correspondingAuthor":false,"prefix":"","firstName":"Yingjie","middleName":"","lastName":"Zhu","suffix":""},{"id":607676946,"identity":"cd5b4c3e-d666-430c-a011-0245b7fbd313","order_by":9,"name":"Yuanping Song","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYFADZiD+wMAGZksQrYVxBmlaQLp4oAy8WuTbew+/5m2zyzNn5z382uYPX+KGA8wHb/Mw2OXh0mJw5lyaNW9bcrFlM1+adQ4Pm7HBAbZkax6G5GKcWiRyzIx525gTNxzmMTPOkWCTMzjAYybNw3AgsQGXw2aAtdRDtFgYsPEYHOD/hlcLw40c48e8bYdBWowfMySAbWHDq8XgzBkzxjnnjifubOYxY+w5wGYseZjN2HKOQTJuh7X3GH94U1aduJ3/jPGHH3+OJfYdb354402FHW6HMTCwSYGiwwDIAEbHMUgyAHHxAOaPPyBqmD8wMNTgVToKRsEoGAUjEwAAgUNQ+Bz59EgAAAAASUVORK5CYII=","orcid":"","institution":"Jiaxing University","correspondingAuthor":true,"prefix":"","firstName":"Yuanping","middleName":"","lastName":"Song","suffix":""}],"badges":[],"createdAt":"2026-02-19 03:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8913489/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8913489/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104998911,"identity":"ba673ba7-5fad-406e-b985-76b8b19cc5b5","added_by":"auto","created_at":"2026-03-19 16:31:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":360169,"visible":true,"origin":"","legend":"\u003cp\u003eCase-report timeline summarizing the chronological sequence of symptom onset, diagnostic work-up, surgical intervention, and post-operative management.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8913489/v1/643b407fddc533dd5688b9cb.png"},{"id":104998912,"identity":"a55a4ebe-c12f-4aa1-b4cf-5936abd497f5","added_by":"auto","created_at":"2026-03-19 16:31:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":14235622,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Multimodality imaging of synchronous pelvic masses. Top row: the right adnexal mass (161.4 × 107.1 × 137.7 mm) and the left adnexal mass (maximal axial dimensions 135.5 × 74.9 mm). Bottom row: tumour invasion; Red arrows indicate tumour infiltration of the sigmoid colon, rectum, and uterus. (B) Histopathology and immunohistochemical profile of resected specimens. Top row: gastric-type endocervical adenocarcinoma—HE, ER, p53, Ki-67, and p16. Middle and bottom rows: high-grade serous ovarian carcinoma—HE, ER, aberrant heterogeneous p53, Ki-67, PR, HER2, and intact mismatch-repair proteins (MLH1, MSH2, MSH6, PMS2). Scale bar = 200 μm.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8913489/v1/4293284c94187755e7547c16.png"},{"id":104998937,"identity":"4ac45dbb-b021-4c8e-9a79-3e823beeba98","added_by":"auto","created_at":"2026-03-19 16:32:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2371752,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8913489/v1/80897eb8-470f-43e3-b8ea-d836a80de281.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synchronous TP53-Aberrant Ovarian and Cervical Carcinomas in a Patient with Parkinson’s Disease: Molecular Insights and Clinical Challenges","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eOvarian high-grade serous carcinoma (HGSC) is the most common and lethal histological subtype of epithelial ovarian cancer, accounting for approximately 70% of ovarian cancer deaths\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003eThe majority of HGSCs are now believed to originate from the fallopian tube epithelium\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, characterized nearly universally by TP53 mutations and frequently associated with homologous recombination deficiency (HRD), particularly in carriers of BRCA1 or BRCA2 pathogenic variants\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. This molecular profile has profound therapeutic implications, notably sensitivity to platinum-based chemotherapy and PARP inhibitors\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Concurrently, primary gastric-type endocervical adenocarcinoma (GEA) represents a rare, aggressive variant, accounting for less than 10% of all cervical adenocarcinomas\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. It is notably unrelated to high-risk human papillomavirus (HPV) infection and is instead associated with mutations in STK11, ERBB2, and occasionally TP53, exhibiting a distinct clinical behavior characterized by late recurrence and poor response to conventional therapies\u003csup\u003e[\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe synchronous occurrence of dual primary gynecologic malignancies, particularly HGSC and GEA, is exceptionally rare. Current literature is sparse, primarily limited to isolated case reports, and the molecular relationship between these two distinct entities remains largely unexplored. A critical unanswered question is whether their co-occurrence is a stochastic event or suggests an underlying shared oncogenic pathway, such as a common germline or somatic predisposition involving TP53 or other DNA damage response genes. Furthermore, the clinical management of such complex cases is not standardized, posing significant challenges in staging, treatment prioritization, and long-term surveillance.\u003c/p\u003e \u003cp\u003eThis case report delineates the unique clinical, pathological, and molecular features of a 67-year-old woman with a 6-year history of Parkinson\u0026rsquo;s disease who presented with synchronous bilateral ovarian HGSC and a primary gastric-type endocervical adenocarcinoma. Comprehensive immunohistochemical profiling revealed aberrant p53 expression (heterogeneous pattern) and a high proliferative index (Ki-67\u0026thinsp;~\u0026thinsp;80%) in both neoplasms, strongly suggestive of concurrent TP53 mutagenesis and a potential common oncogenic driver, possibly within the BRCA/TP53 axis. This molecular convergence in two morphologically and anatomically distinct tumors presents a compelling argument for a shared genetic etiology rather than a mere coincidence. The presence of significant comorbidities, namely Parkinson\u0026rsquo;s disease, introduces an additional layer of complexity to the perioperative and systemic management of this elderly patient, influencing decisions regarding chemotherapy tolerance, potential drug interactions with levodopa, and overall functional reserve. Therefore, this case serves two primary purposes: First, it provides a detailed clinicopathological description of a highly unusual dual malignancy, enriching the limited literature on such synchronous presentations. Second, it proposes a hypothesis of a unified molecular pathogenesis, underscoring the critical role of comprehensive genetic testing (including BRCA1/2 and TP53) in explaining carcinogenesis and guiding targeted therapeutic strategies. By highlighting the diagnostic challenges, therapeutic dilemmas, and molecular insights, this report aims to contribute to the understanding of rare tumor associations and advocate for personalized, genotype-driven management in complex oncological scenarios.\u003c/p\u003e"},{"header":"2. Presentation of case","content":"\u003cp\u003eA 67-year-old female with a 6-year history of Parkinson\u0026rsquo;s disease, maintained on levodopa\u0026ndash;benserazide (0.125 g orally three times daily), presented with a 6-month history of lower abdominal distension and altered bowel habits, followed by 15 days of persistent dull lower abdominal pain accompanied by bloating and difficulty defecating. She was admitted for further evaluation.\u003c/p\u003e \u003cp\u003eLaboratory investigations revealed significantly elevated tumor markers: HE4 932.70 pmol/L, CA-125 1579.09 U/mL, and CA-153 366.70 U/mL. Imaging studies, including abdominal CT and pelvic MRI, identified large bilateral adnexal complex cystic-solid masses (left: 75\u0026times;137\u0026times;65 mm; right: 107\u0026times;137\u0026times;161 mm), highly suggestive of malignancy with involvement of the uterus, sigmoid colon, and rectum. A chest CT revealed a small nodule in the right upper lobe. Colonoscopy showed colonic polyps, and gastroscopy indicated chronic active atrophic gastritis (C-1). Cervical screening (HPV and TCT) was negative.\u003c/p\u003e \u003cp\u003eThe patient underwent exploratory laparotomy in February 2025, which revealed approximately 50 mL of ascitic fluid, bilateral enlarged ovaries adherent to surrounding structures, and miliary nodules on the omentum. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and adhesiolysis.\u003c/p\u003e \u003cp\u003eFinal pathology confirmed: 1. Bilateral high-grade serous ovarian carcinoma with lymphovascular invasion and involvement of the left fallopian tube, appendix, and omentum; 2. Primary gastric-type endocervical adenocarcinoma (non-HPV related), with superficial myometrial invasion; 3. Concurrent benign findings including uterine adenomatoid tumor, leiomyoma with calcification, and endometrial polyp.\u003c/p\u003e \u003cp\u003eImmunohistochemical profiling supported a BRCA/p53-related pathway abnormality, with heterogeneous p53 expression, high Ki-67 (80%+), and mismatch repair proficiency. The patient is currently recovering postoperatively, with plans for genetic testing and adjuvant therapy.\u003c/p\u003e \u003cp\u003eIn summary, the entire clinical course of this case\u0026mdash;from symptom onset, through imaging and laboratory investigations, surgical intervention, to postoperative pathological assessment and treatment planning\u0026mdash;can be outlined in the following timeline(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"3. Discussion","content":"\u003cp\u003eThis report presents a diagnostically and therapeut complex case of a 67-year-old female with Parkinson\u0026rsquo;s disease who was diagnosed with synchronous primary malignancies: bilateral high-grade serous ovarian carcinoma (HGSC) and gastric-type endocervical adenocarcinoma (GEA). The patient exhibited markedly elevated tumor markers and radiographic signs of local invasion. She underwent comprehensive surgical resection, with pathological examination confirming advanced HGSC with transcoelomic dissemination and a concurrent HPV-independent cervical adenocarcinoma showing superficial invasion. This case is particularly notable due to the exceptionally rare co-occurrence of two histologically and etiologically distinct gynecologic malignancies, both demonstrating immunohistochemical evidence of TP53 dysfunction, in a patient with a pre-existing neurodegenerative disorder. This unusual presentation raises compelling questions regarding potential shared oncogenic pathways, such as BRCA/TP53 aberrations, and underscores the salient challenges in geriatric oncology care for patients with significant comorbidities. Consequently, this case provides valuable clinical insights and serves as an instructive example regarding multimodal diagnostics, the role of genetic profiling in elucidating cancer etiology, and the complexities of treatment planning in the context of concurrent chronic illness.\u003c/p\u003e \u003cp\u003eThe patient initially presented with lower abdominal pressure and pain. Imaging, histopathological, and immunohistochemical analyses confirmed synchronous bilateral ovarian HGSC and cervical GEA, representing a rare instance of dual primary malignancy. Ovarian HGSC, the most common and aggressive form of epithelial ovarian cancer, is frequently associated with TP53 mutations and BRCA pathway abnormalities\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In this case, the bilateral ovarian tumors were large, with invasion into adjacent structures, ascites, and omental metastasis, consistent with typical HGSC behavior. Simultaneously, the patient was diagnosed with cervical GEA, a rare HPV-independent adenocarcinoma accounting for approximately 10%\u0026ndash;15% of all cervical adenocarcinomas. This tumor type exhibits morphological and immunophenotypic characteristics\u0026mdash;such as MUC6 and HIK1083 positivity\u0026mdash;resembling gastric epithelium\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. GEA is generally aggressive, carries a poor prognosis, and occurs more frequently in older women\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eNotably, both malignancies showed aberrant p53 expression, a high Ki-67 proliferation index (approximately 80%), and discordant ER/PR receptor status, suggesting possible common oncogenic mechanisms. Immunohistochemical analysis revealed retained expression of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2), effectively excluding Lynch syndrome and further supporting a potential role for BRCA1/2 or TP53 mutations in tumor development \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough ovarian high-grade serosa carcinoma (HGSC) and GEA originate from distinct histological lineages, the shared observation of aberrant p53 expression implies that TP53 mutation may contribute significantly to their synchronous occurrence. Moreover, although BRCA mutations are frequently identified in HGSC, they have also been reported in certain cases of GEA\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. The immunohistochemical profile in this patient suggests that both malignancies may involve dysregulation within the BRCA/TP53 pathway. Further investigation utilizing next-generation sequencing (NGS) to assess the mutation status of BRCA1/2 and TP53 is warranted to elucidate whether these tumors are clonally related\u0026mdash;derived from a common progenitor cell\u0026mdash;or represent independent primary malignancies. The identification of identical pathogenic mutations in both tumors would support a clonal origin, whereas divergent genetic profiles would indicate independent tumorigenesis. This distinction bears substantial clinical relevance, as clonally related tumors may exhibit susceptibility to PARP inhibitors, while independently arising tumors would necessitate tailored therapeutic approaches \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe patient initially reported six months of \u0026ldquo;discomfort and a sensation of pressure in the lower abdomen,\u0026rdquo; accompanied by changes in bowel habits. These symptoms progressed to persistent lower abdominal pain and distension. Such nonspecific manifestations can easily mimic benign pelvic conditions\u0026mdash;such as ovarian cysts, uterine fibroids, or pelvic inflammatory disease\u0026mdash;or functional gastrointestinal disorders\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. In elderly patients especially, gastrointestinal symptoms are often attributed to age-related functional changes or common entities like constipation or irritable bowel syndrome, frequently resulting delayed diagnosis of malignancy\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. This case underscores the importance of considering occult gynecologic malignancies\u0026mdash;including ovarian cancer and non-HPV-associated cervical adenocarcinomas\u0026mdash;in cases of persistent pelvic discomfort accompanied by bowel habit changes, even when initial evaluations are unremarkable. Abdominal-pelvic CT and MRI were instrumental in the initial assessment of tumor extent, local invasion, and lymph node involvement. CT imaging demonstrated large, complex cystic-solid pelvic masses bilaterally with invasion into adjacent structures. MRI provided superior delineation of anatomical relationships with adjacent organs such as the sigmoid colon, rectum, and posterior uterine wall, while also revealing features suggestive of malignancy, including restricted diffusion and prominent contrast enhancement \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, although imaging findings were highly indicative of malignancy, they lacked the specificity required to differentiate between synchronous primary carcinomas and metastatic spread, or to determine the exact histological subtype\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. Definitive diagnosis remains dependent on thorough histopathological and immunohistochemical evaluation. These imaging and immunohistochemical features are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Panel A shows the complex cystic-solid masses in the bilateral adnexal regions seen on pelvic MRI and CT, with invasion into adjacent structures. Panel B displays the corresponding histopathological sections (hematoxylin and eosin [H\u0026amp;E] staining) for the cervical gastric-type adenocarcinoma and the ovarian high-grade serous carcinoma, alongside the expression profiles of key immunohistochemical markers (p53, Ki-67, p16, estrogen receptor [ER], progesterone receptor [PR], HER2, and mismatch repair proteins).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eGEA is a rare but highly aggressive subtype of cervical cancer that is not associated with human papillomavirus (HPV) infection. It occurs predominantly in elderly women and often presents with non-specific symptoms, frequently leading to oversight or misdiagnosis\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. In the present case, the patient\u0026rsquo;s cervical screening\u0026mdash;including HPV testing and cytology\u0026mdash;yielded unremarkable results; nevertheless, she was postoperatively diagnosed with GEA based on histopathological findings. This underscores that even with normal cervical morphology and cytology, the possibility of a non-HPV-associated adenocarcinoma cannot be ruled out. Additionally, the patient was diagnosed with a concurrent ovarian high-grade serous carcinoma (HGSC). Although these two malignancies may share molecular alterations such as TP53 or BRCA mutations, a careful distinction must be made between synchronous primary carcinomas and metastatic disease\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Such cases highlight the importance of maintaining a broad differential diagnosis when evaluating complex pelvic masses. A comprehensive diagnostic approach incorporating imaging, tumor marker assays, and intraoperative frozen section analysis is essential. When warranted, immunohistochemical staining and molecular profiling should be promptly employed to establish a definitive diagnosis.\u003c/p\u003e \u003cp\u003eFor advanced epithelial ovarian cancer, primary debulking surgery (PDS) represents a cornerstone of treatment with the goal of achieving long-term survival. Intraoperative assessment in this case revealed extensive pelvic and abdominal disease, including omental metastasis, but no evidence of distant lymph node or parenchymal organ involvement. The patient therefore underwent comprehensive cytoreductive surgery, comprising total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and lysis of intestinal adhesions. Although complete macroscopic resection (R0) was not attained due to suspected residual disease on intestinal surfaces, maximal effort toward optimal (R1) cytoreduction is a critical prognostic factor\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Notably, the patient also had a concurrent diagnosis of GEA\u0026mdash;a tumor type generally resistant to radiotherapy and conventional chemotherapy, for which surgical resection remains the primary treatment\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. Thus, the extensive surgical intervention was appropriate for addressing both the ovarian carcinoma and the synchronous cervical GEA. Postoperative adjuvant therapy should be tailored according to the final FIGO staging.\u003c/p\u003e \u003cp\u003eOvarian high-grade serous carcinoma (HGSC) is typically sensitive to platinum-based agents, with carboplatin plus paclitaxel constituting first-line adjuvant chemotherapy\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Immunohistochemical results showing aberrant p53 expression and a high Ki-67 proliferation index suggest an underlying TP53 mutation. Further genetic evaluation for BRCA1/2 mutations and homologous recombination deficiency (HRD) status is recommended to assess potential susceptibility to poly-ADP ribose polymerase (PARP) inhibitors. Should a BRCA mutation or HRD be confirmed, maintenance therapy with a PARP inhibitor such as olaparib may be indicated, as this approach has been shown to significantly prolong progression-free survival. In contrast, GEA generally exhibits poor response to conventional chemoradiation, necessitating a more individualized therapeutic strategy. In this case, HER2 (ErbB-2) immunohistochemistry was scored 1+. If fluorescence in situ hybridization (FISH) confirms HER2 amplification, targeted therapy with anti-HER2 agents such as trastuzumab could be considered. Moreover, GEA is frequently associated with mutations in genes such as STK11 and KRAS. Comprehensive genomic profiling via next-generation sequencing (NGS) is therefore advised to identify additional potential therapeutic targets, including alterations amenable to targeted agents such as mTOR inhibitors\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe prognosis of synchronous primary malignancies is influenced by multiple factors, including tumor stage, histological type, molecular characteristics, and the patient\u0026rsquo;s performance status\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e. In this case, the ovarian cancer involved the omentum, appendix, and fallopian tubes, with lymphovascular space invasion indicating a FIGO stage of at least III, which is associated with an unfavorable prognosis. Although the cervical gastric-type adenocarcinoma was limited to the superficial myometrium, it exhibits more aggressive biological behavior than conventional cervical adenocarcinoma and is associated with a propensity for late recurrence\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Immunohistochemical analysis demonstrated aberrant p53 expression, a high Ki-67 proliferation index (approximately 80%), and discordant estrogen receptor (ER) and progesterone receptor (PR) expression. These features are consistent with high-grade serous carcinoma and suggest possible TP53 and BRCA1/2 mutations\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Although such tumors are generally sensitive to platinum-based chemotherapy, they carry a high risk of recurrence. Genetic counseling and testing are therefore advised to assess eligibility for PARP inhibitor therapy. Additionally, the tumor exhibited retained/positive expression of all mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6), effectively excluding Lynch syndrome. Nonetheless, other genetic susceptibility factors should still be investigated.\u003c/p\u003e \u003cp\u003eA primary limitation is the single-case design. Although the patient received comprehensive preoperative evaluation, successful surgical treatment, and detailed postoperative histopathological and immunohistochemical assessment, the findings and conclusions drawn from a single case have inherently limited generalizability. Whether common patterns exist in the pathogenesis, clinical behavior, and treatment responses of synchronous primary malignancies requires validation through larger clinical studies. Moreover, the patient\u0026rsquo;s comorbid Parkinson\u0026rsquo;s disease likely affected her treatment tolerance and prognosis, a factor that may not be common among other patients. This case also highlights promising avenues for further investigation. The two malignancies may share alterations in molecular pathways such as BRCA/p53. Although this hypothesis is supported by immunohistochemical results\u0026mdash;including aberrant p53 expression and a high Ki-67 index\u0026mdash;it lacks confirmation through direct genetic sequencing. Therefore, we recommend future large-scale, multi-center cohort studies of synchronous primary gynecological cancers incorporating systematic next-generation sequencing (e.g., whole-exome sequencing). Such research is crucial for elucidating common oncogenic drivers, clonal evolutionary relationships, and tumor microenvironment features. This approach would help clarify whether these tumors are clonally related or independent, and could inform the development of precision treatments targeting shared pathways, such as PARP inhibitor therapy. Finally, genetic testing results for this case are still pending, constituting a notable limitation but also suggesting a clear avenue for subsequent investigation. Once germline and somatic mutation statuses of BRCA1/2 and \u003cem\u003eTP53\u003c/em\u003e are confirmed, future analyses should focus on correlating these genetic alterations with the patient\u0026rsquo;s response to platinum-based chemotherapy, targeted agents, progression-free survival (PFS), and overall survival (OS). Such correlation will help validate current hypotheses regarding molecular subtype-guided therapy and contribute to the development of more individualized prognostic models and treatment strategies for this patient population.\u003c/p\u003e \u003cp\u003eIn summary, this case underscores the importance of maintaining a high index of suspicion for both HPV-independent cervical carcinomas and synchronous primary malignancies. Despite its limitations, it offers a useful framework for future mechanistic research and clinical decision-making. We encourage collaborative efforts within the research community to improve outcomes for patients with such rare and complex gynecologic tumors through the accumulation of larger case series, prospective molecular profiling, and the establishment of comprehensive clinical databases with long-term follow-up.\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eThis rare case of synchronous TP53-aberrant HGSC and GEA suggests a potential common oncogenic driver, warranting comprehensive genetic profiling (e.g., BRCA1/2, TP53) to clarify clonality and guide targeted therapy. The coexistence of Parkinson\u0026rsquo;s disease further underscores the need for individualized treatment strategies. We advocate for integrated molecular diagnostics in patients with atypical pelvic presentations to optimize management of such complex malignancies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHGSC \u0026nbsp; \u0026nbsp;High-grade Serous Carcinoma\u003c/p\u003e\n\u003cp\u003eGEA \u0026nbsp; \u0026nbsp; Gastric-type Endocervical Adenocarcinoma\u003c/p\u003e\n\u003cp\u003eHRD \u0026nbsp; \u0026nbsp; Homologous Recombination Deficiency\u003c/p\u003e\n\u003cp\u003eHPV \u0026nbsp; \u0026nbsp; Human Papillomavirus\u003c/p\u003e\n\u003cp\u003eCT \u0026nbsp; \u0026nbsp; \u0026nbsp;Computed Tomography\u003c/p\u003e\n\u003cp\u003eMRI \u0026nbsp; \u0026nbsp; Magnetic Resonance Imaging\u003c/p\u003e\n\u003cp\u003eBRCA \u0026nbsp; Breast cancer gene\u003c/p\u003e\n\u003cp\u003eER \u0026nbsp; \u0026nbsp; \u0026nbsp;Estrogen Receptor\u003c/p\u003e\n\u003cp\u003ePR \u0026nbsp; \u0026nbsp; \u0026nbsp;Progesterone Receptor\u003c/p\u003e\n\u003cp\u003ePDS \u0026nbsp; \u0026nbsp; Primary Debulking Surgery\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePARP \u0026nbsp; \u0026nbsp;Poly-ADP Ribose Polymerase\u003c/p\u003e\n\u003cp\u003eNGS \u0026nbsp; \u0026nbsp; Next-generation Sequencing\u003c/p\u003e\n\u003cp\u003eMMR \u0026nbsp; \u0026nbsp;Mismatch Mepair\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePFS \u0026nbsp; \u0026nbsp; Progression-free Survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOS \u0026nbsp; \u0026nbsp; \u0026nbsp;Overall Survival\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eC.W. conceptualized the study, collected clinical data, and wrote the original draft. S.P. coordinated the project and reviewed the manuscript. K.W. and A.W. assisted in clinical data collection and analysis. J.Z. and Q.C. performed data analysis and interpretation. W.Z. conducted pathological examinations and provided all pathological images.Y.Z. and Y.S. contributed to literature review and data curation. Y.S. supervised the research, revised the manuscript critically, and acted as corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report and its accompanying images were published with the written informed consent of the patient\u0026apos;s relative. The consent form is available for review by the Editor-in-Chief upon request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003enull. Integrated genomic analyses of ovarian carcinoma[J]. Nature. 2011;474(7353):609\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nature10166\u003c/span\u003e\u003cspan address=\"10.1038/nature10166\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKurman RJ, Shih I. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer\u0026ndash;shifting the paradigm[J]. 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Curr Issues Mol Biol. 2024;46(9):9376\u0026ndash;85. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cimb46090555\u003c/span\u003e\u003cspan address=\"10.3390/cimb46090555\" targettype=\"DOI\" class=\"RefTarget\"\u003e\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":false,"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":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ovarian high-grade serous carcinoma, Gastric-type endocervical adenocarcinoma, PARP inhibitors, Case report","lastPublishedDoi":"10.21203/rs.3.rs-8913489/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8913489/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe synchronous occurrence of bilateral ovarian high-grade serous carcinoma (HGSC) and primary gastric-type endocervical adenocarcinoma (GEA) is exceedingly rare, with limited understanding of their molecular relationship and clinical management. This report presents a unique case of dual primary gynecologic malignancies in a patient with Parkinson\u0026rsquo;s disease, highlighting diagnostic challenges, therapeutic complexities, and potential shared oncogenic pathways.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eA 67-year-old female with a 6-year history of Parkinson\u0026rsquo;s disease presented with lower abdominal distension, pain, and altered bowel habits. Imaging revealed bilateral adnexal masses with local invasion. Surgical resection confirmed synchronous bilateral HGSC (FIGO stage III) and GEA (superficial myometrial invasion), both exhibiting aberrant p53 expression (heterogeneous pattern), high Ki-67 (\u0026sim;80%), and mismatch repair proficiency. Immunohistochemical profiling suggested involvement of the BRCA/TP53 pathway.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case underscores the rarity of synchronous HGSC and GEA, both demonstrating TP53 dysfunction, potentially indicating a common molecular etiology. Comprehensive genetic testing (e.g., BRCA1/2, TP53) is critical to elucidate clonality and guide targeted therapy. The presence of Parkinson\u0026rsquo;s disease further complicates management, emphasizing the need for personalized, multimodal treatment strategies. This report advocates for heightened clinical suspicion of synchronous malignancies in patients with persistent pelvic symptoms and supports integrated molecular profiling to optimize therapeutic outcomes.\u003c/p\u003e","manuscriptTitle":"Synchronous TP53-Aberrant Ovarian and Cervical Carcinomas in a Patient with Parkinson’s Disease: Molecular Insights and Clinical Challenges","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-19 16:31:40","doi":"10.21203/rs.3.rs-8913489/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-09T18:11:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286772072518696782045947397454304917340","date":"2026-03-27T09:36:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-17T11:38:38+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-16T13:36:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-23T15:02:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-22T03:09:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2026-02-22T03:05:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5015791f-8e17-4df6-915f-79dd2350e468","owner":[],"postedDate":"March 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-19T16:31:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-19 16:31:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8913489","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8913489","identity":"rs-8913489","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}