Mismatch Repair Gene Deficiency in Ovarian Cancer: A Clinicopathological Analysis of MLH1, PMS2, MSH2, and MSH6...

Mismatch repair (MMR) deficiency is a prognostic biomarker in multiple malignancies, but its clinical significance in ovarian cancer (OC) remains poorly defined. This study investigates the prevalence of MMR gene defects (MLH1, PMS2, MSH2, MSH6) across OC histotypes and their clinicopathological associations.

A retrospective cohort of 38 OC patients treated at Azerbaijan Medical University (2018-2023) underwent immunohistochemical (IHC) analysis of MMR protein expression. Clinicopathological data, including survival, recurrence, tumor characteristics, and biomarker status (Ki67, p53), were analyzed using SPSS v26.0. MMR deficiency was defined as loss of nuclear expression in ≥1 protein.

MMR deficiency was identified in 5.2% of cases (2/38), restricted to endometrioid carcinomas (33.3% of endometrioid cases, 2/6). No deficiencies occurred in serous (n=27), clear cell (n=2), or mixed subtypes (n=3). Endometrioid tumors exhibited larger mean tumor size (13.7 ±5.2 cm vs. 10.0 ±3.7 cm in serous; p=0.01) and distinct Ki67/p53 expression patterns (p<0.05). Despite 55.3% overall mortality (21/38), MMR-deficient cases showed no recurrence or mortality. Serous carcinomas had the highest recurrence (37.0%, 10/27) and mortality rates (70.4%, 19/27). Five-year survival was 81.6%, with no significant association between MMR status and survival (p>0.05).

MMR deficiency in OC is histotype-dependent, occurring exclusively in endometrioid carcinomas. While not prognostic in this cohort, dMMR screening may guide surveillance for synchronous malignancies and identify candidates for immunotherapy. Multicenter studies with expanded cohorts are needed to validate clinical utility.