Open Access

REVIEW

Molecular Pathology of Ovarian Endometrioid Carcinoma: A Review

Hiroshi Yoshida^1,*, Mayumi Kobayashi Kato²

1 Department of Diagnostic Pathology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
2 Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

* Corresponding Author: Hiroshi Yoshida. Email:

Oncology Research 2025, 33(12), 3701-3730. https://doi.org/10.32604/or.2025.068432

Received 28 May 2025; Accepted 22 September 2025; Issue published 27 November 2025

Abstract

Ovarian endometrioid carcinoma (OEC) accounts for ~10% of epithelial ovarian cancers and displays broad morphologic diversity that complicates diagnosis and grading. Recent data show that the endometrial cancer molecular taxonomy (DNA polymerase epsilon, catalytic subunit [POLE]-ultramutated, mismatch repair-deficient [MMRd], p53-abnormal, no specific molecular profile [NSMP]) also applies to OEC, and that OEC is enriched for Lynch syndrome–associated tumors, supporting routine MMR testing. We aimed to synthesize contemporary evidence spanning epidemiology, histopathology and immunophenotype, diagnostic pitfalls and differential diagnosis, and to evaluate the clinical utility of The Cancer Genome Atlas (TCGA)-surrogate molecular classification for risk stratification; we also summarize implications for Lynch screening, genetic counseling, and therapeutic opportunities including immune checkpoint inhibitors and targeted approaches, with practical recommendations for diagnostic workflows. Integrating morphology with molecular classification refines diagnosis and prognostication: POLEmut/MMRd subsets generally have excellent outcomes and are candidates for de-escalation or immunotherapy, whereas p53abn/high-grade tumors carry a poorer prognosis and may warrant intensified management and trials of homologous recombination deficiency (HRD)-directed strategies; routine MMR immunohistochemistry (IHC) with reflex germline testing improves Lynch detection, and future priorities include prospective validation and multi-omics to refine NSMP and identify new targets.

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Keywords

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