Mismatch Repair Protein Expression in Endometrial Intraepithelial Neoplasia and Endometrial Carcinoma: Experience...

Endometrial carcinoma is the most common malignancy of the female genital tract, and endometrial intraepithelial neoplasia (EIN, also termed atypical endometrial hyperplasia) is its recognized precursor lesion. Mismatch repair (MMR) deficiency, identified through loss of MLH1, PMS2, MSH2, and MSH6 expression on immunohistochemistry (IHC), is an important molecular event in endometrial carcinogenesis with diagnostic, prognostic, and hereditary (Lynch syndrome) implications. Comparatively few studies have examined the frequency of MMR loss in EIN. This study evaluated the proportion and patterns of MMR protein loss in EIN and endometrial carcinoma, with descriptive assessment of MMR protein loss according to histopathological grade of endometrial carcinoma.

This cross-sectional study was conducted in a tertiary care hospital from August 2024 to December 2025 on 28 endometrial specimens (endometrial biopsies and hysterectomy specimens). These specimens were diagnosed histopathologically as EIN or endometrial carcinoma, collected retrospectively and prospectively using convenience sampling. Formalin-fixed, paraffin-embedded sections were stained with hematoxylin and eosin and evaluated. IHC for MLH1, MSH2, MSH6, and PMS2 was performed on all cases. Complete loss of nuclear staining for any MMR protein with intact internal controls was interpreted as MMR-deficient (dMMR); retained staining for all four proteins was interpreted as MMR-proficient (pMMR). Descriptive assessment of MMR protein loss according to histopathological grade of endometrial carcinoma was also performed.

Of 28 cases, 16 (57.14%) were endometrioid endometrial carcinoma, and 12 (42.86%) were EIN. Patients' ages ranged from 34-68 years; EIN was most common in the sixth decade and carcinoma in the fifth. Among the 16 carcinomas, nine (56.25%) were International Federation of Gynecology and Obstetrics (FIGO) grade 1, six (37.50%) grade 2, and one (6.25%) grade 3. Only one carcinoma (6.25%) was dMMR, showing combined loss of MSH2 and MSH6, and this case was FIGO grade 2. Among the 12 EIN cases, only one (8.33%) was dMMR, showing combined loss of MLH1 and PMS2. All remaining cases in both groups were pMMR.

MMR protein loss was infrequent in this cohort of EIN and endometrial carcinoma, consistent with the broader literature describing MMR deficiency as a relatively uncommon but clinically significant event across the endometrial hyperplasia-carcinoma sequence.