{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:25:54Z","timestamp":1790886354703,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. Results: Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52\u201376 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS &lt; 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38\/42), with a recurrence rate of 39% (26\/67). Conclusion: MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.<\/jats:p>","DOI":"10.3390\/curroncol31090378","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T09:39:32Z","timestamp":1725010772000},"page":"5107-5120","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Ovarian Mesonephric-like Adenocarcinoma: Its Prevalence in a Japanese High-Volume Cancer Center and a Literature Review on Therapeutic Targets"],"prefix":"10.3390","volume":"31","author":[{"given":"Ayako","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7569-7813","authenticated-orcid":false,"given":"Hiroshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saria","family":"Kawano","sequence":"additional","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Kikkawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-0289","authenticated-orcid":false,"given":"Mayumi","family":"Kobayashi-Kato","sequence":"additional","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Tanase","sequence":"additional","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Uno","sequence":"additional","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-2966","authenticated-orcid":false,"given":"Mitsuya","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Gynecology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/his.12895","article-title":"Hormone receptor-negative, thyroid transcription factor 1-positive uterine and ovarian adenocarcinomas: Report of a series of mesonephric-like adenocarcinomas","volume":"68","author":"McFarland","year":"2016","journal-title":"Histopathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/his.13970","article-title":"Endometriosis-related pathology: A discussion of selected uncommon benign, premalignant and malignant lesions","volume":"76","author":"McCluggage","year":"2020","journal-title":"Histopathology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13000-019-0830-4","article-title":"Coexistence of endometrial mesonephric-like adenocarcinoma and endometrioid carcinoma suggests a M\u00fcllerian duct lineage: A case report","volume":"14","author":"Yano","year":"2019","journal-title":"Diagn. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/PAP.0000000000000342","article-title":"Mesonephric-like Adenocarcinoma of the Female Genital Tract: From Morphologic Observations to a Well-characterized Carcinoma with Aggressive Clinical Behavior","volume":"29","author":"McCluggage","year":"2022","journal-title":"Adv. Anat. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/PAS.0000000000001612","article-title":"Clinicopathologic Characteristics of Mesonephric Adenocarcinomas and Mesonephric-like Adenocarcinomas in the Gynecologic Tract: A Multi-institutional Study","volume":"45","author":"Pors","year":"2021","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1177\/10668969231183631","article-title":"Ovarian Mesonephric-Like Adenocarcinoma with Recurrent Liver Metastases: A Case Report with Analysis of Therapeutic Molecular Targets","volume":"32","author":"Sugitani","year":"2024","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/PAS.0000000000000958","article-title":"Targeted Genomic Profiling Reveals Recurrent KRAS Mutations in Mesonephric-like Adenocarcinomas of the Female Genital Tract","volume":"42","author":"Mirkovic","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1097\/PAS.0000000000001142","article-title":"A Comparison of GATA3, TTF1, CD10, and Calretinin in Identifying Mesonephric and Mesonephric-like Carcinomas of the Gynecologic Tract","volume":"42","author":"Pors","year":"2018","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/PGP.0000000000000444","article-title":"An Ovarian Adenocarcinoma with Combined Low-grade Serous and Mesonephric Morphologies Suggests a M\u00fcllerian Origin for Some Mesonephric Carcinomas","volume":"37","author":"Chapel","year":"2018","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/PGP.0000000000000573","article-title":"Ovarian Combined Low-grade Serous and Mesonephric-like Adenocarcinoma: Further Evidence for A Mullerian Origin of Mesonephric-like Adenocarcinoma","volume":"39","author":"McCluggage","year":"2020","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13000-020-01012-z","article-title":"Ovarian mesonephric-like adenocarcinoma arising in serous borderline tumor: A case report with complex morphological and molecular analysis","volume":"15","author":"Dundr","year":"2020","journal-title":"Diagn. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100657","DOI":"10.1016\/j.gore.2020.100657","article-title":"Mesonephric-like adenocarcinoma of the ovary with co-existent endometriosis: A case report and review of the literature","volume":"34","author":"Seay","year":"2020","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e23450","DOI":"10.1097\/MD.0000000000023450","article-title":"Mesonephric-like adenocarcinoma of the ovary: A case report and a review of the literature","volume":"99","author":"Chen","year":"2020","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E207","DOI":"10.1002\/dc.24675","article-title":"Cytohistopathologic correlation of ovarian mesonephric-like carcinoma and female adnexal tumor of probable Wolffian origin","volume":"49","author":"Qazi","year":"2021","journal-title":"Diagn. Cytopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/s41379-021-00799-6","article-title":"Mesonephric and mesonephric-like carcinomas of the female genital tract: Molecular characterization including cases with mixed histology and matched metastases","volume":"34","author":"Fix","year":"2021","journal-title":"Mod. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.21873\/invivo.12667","article-title":"Ovarian Mesonephric-like Adenocarcinoma with Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated with Ovarian High-grade Serous Carcinoma","volume":"35","author":"Kim","year":"2021","journal-title":"In Vivo"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.pathol.2021.09.007","article-title":"Ovarian mesonephric-like adenocarcinoma: Morphological diversity and histogenetic considerations of an unusual tumour","volume":"54","author":"Karpathiou","year":"2022","journal-title":"Pathology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1111\/jog.15035","article-title":"Mesonephric-like adenocarcinoma of the ovary in an elderly woman: A case report and a review of the literature","volume":"47","author":"Ujita","year":"2021","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/PAS.0000000000001766","article-title":"Extrauterine Mesonephric-like Neoplasms: Expanding the Morphologic Spectrum","volume":"46","author":"Deolet","year":"2022","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Koh, H.H., Park, E., and Kim, H.S. (2022). Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020326"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/jog.15539","article-title":"Synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma: A case report","volume":"49","author":"Ishida","year":"2023","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101049","DOI":"10.1016\/j.gore.2022.101049","article-title":"Somatic mutation analysis of Mesonephric-Like adenocarcinoma and associated putative precursor Lesions: Insight into pathogenesis and potential molecular treatment targets","volume":"42","author":"Arslanian","year":"2022","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1097\/PAS.0000000000001903","article-title":"Mucinous Tumor Coexisting with Mesonephric-like Proliferation\/Tumor in the Ovary: A Novel Association","volume":"46","author":"Nilforoushan","year":"2022","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1111\/his.14892","article-title":"Mesonephric-like adenocarcinoma of the female genital tract: Novel observations and detailed molecular characterisation of mixed tumours and mesonephric-like carcinosarcomas","volume":"82","author":"Mirkovic","year":"2023","journal-title":"Histopathology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s00428-023-03522-9","article-title":"Mesonephric-like adenocarcinoma of the ovary with squamoid morular metaplasia, aberrant \u03b2-catenin expression, and concurrent FGFR2 and CTNNB1 mutations: A case report","volume":"484","author":"Xu","year":"2024","journal-title":"Virchows Arch."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/PGP.0000000000000868","article-title":"Ovarian Combined Serous Borderline Tumor\/Low-grade Serous Carcinoma and Mesonephric-like Lesion: Report of 2 Cases with New Observations","volume":"42","author":"Nilforoushan","year":"2023","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1097\/PGP.0000000000000935","article-title":"Ovarian RASoma With Mesonephric-like Adenocarcinoma and Mixed Mullerian Components: A Case Report with Molecular Analysis Demonstrating Multidirectional Mullerian Differentiation","volume":"42","author":"Stolnicu","year":"2023","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/path.6217","article-title":"Mesonephric-like adenocarcinoma harbours characteristic copy number variations and a distinct DNA methylation signature closely related to mesonephric adenocarcinoma of the cervix","volume":"262","author":"Kommoss","year":"2024","journal-title":"J. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/PGP.0000000000000997","article-title":"Synchronous Bilateral Ovarian Mesonephric-like Adenocarcinomas with Separate Origins from High-Grade Mullerian Adenosarcoma and Endometriosis: Report of a Rare Case","volume":"43","author":"Zhao","year":"2024","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/PGP.0000000000000863","article-title":"Two Cases of Mesonephric-like Carcinoma Arising from Endometriosis: Case Report and Review of the Literature","volume":"42","author":"Chang","year":"2023","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00531","DOI":"10.1016\/j.crwh.2023.e00531","article-title":"Mesonephric-like adenocarcinoma arising from endometrioid adenofibroma in a patient with in-utero exposure to diethylstilbestrol: A case report","volume":"39","author":"Linck","year":"2023","journal-title":"Case Rep. Women\u2019s Health"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1177\/10668969231213390","article-title":"Mixed Mesonephric-like Adenocarcinoma, Clear Cell Carcinoma, and Endometrioid Carcinoma Arising from an Endometriotic Cyst","volume":"32","author":"Nagase","year":"2023","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/PAS.0000000000001193","article-title":"A Combined Morphologic and Molecular Approach to Retrospectively Identify KRAS-Mutated Mesonephric-like Adenocarcinomas of the Endometrium","volume":"43","author":"Kolin","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/jnci\/djy071","article-title":"Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage","volume":"111","author":"Peres","year":"2019","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1136\/ijgc-2021-003112","article-title":"The effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, grade 1 and 2 endometrioid ovarian carcinoma","volume":"32","author":"Swift","year":"2022","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pathol.2020.10.007","article-title":"Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: A guide to immunohistochemistry implementation and interpretation","volume":"53","author":"Paver","year":"2021","journal-title":"Pathology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ygyno.2021.10.078","article-title":"Clinical factors and biomarker profiles associated with patient outcome in endometrioid ovarian carcinoma\u2014Emphasis on tumor grade","volume":"164","author":"Soovares","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e450s","DOI":"10.6061\/clinics\/2018\/e450s","article-title":"Homologous recombination deficiency in ovarian cancer: A review of its epidemiology and management","volume":"73","author":"Fogace","year":"2018","journal-title":"Clinics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","article-title":"Sotorasib for Lung Cancers with","volume":"384","author":"Skoulidis","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2203690","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer","volume":"387","author":"Modi","year":"2022","journal-title":"N. Engl. J. Med."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/9\/378\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:45:33Z","timestamp":1760111133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/9\/378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,30]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["curroncol31090378"],"URL":"https:\/\/doi.org\/10.3390\/curroncol31090378","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,30]]}}}