Study of Immunohistochemical Expression Patterns of Mismatch Repair Proteins in Endometrial Carcinoma and Endometrial Hyperplasia: An Institutional Study

Abstract Introduction Endometrial carcinoma (EC) is the most common cancer in women (7% of all malignancies) standing fourth in prevalence. Its molecular categorization has lately gained substantial importance, because of its prognostic implications and association of mismatch repair (MMR) proteins with Lynch syndrome. Objectives Our aim of the study was to analyze the expression of MMR proteins (MLH1, PMS2, MSH6, MSH2) in EC and Endometrial hyperplasia (EH). Materials and Methods This study was performed on 52 EC and 65 EH cases (7 cases - disordered proliferative endometrium, 12 cases - EH with atypia, 46 cases - EH without atypia). Immunohistochemical staining with MLH1, PMS2, MSH6, and MSH2 were performed. SSPS software version 25 with chi-square test was used in statistical analysis. Results Out of 52 cases of EC, 42 (80.76%) cases were identified as MMRd.MLH1 negative expression, which was significant (p: 0.005) compared with other markers. Also, there was significant statistical correlation (p: 0.004) between lower International Federation of Gynecology and Obstetrics grade and MLH1/PMS2 loss. Only six cases of EC had notable family history. Of 12 cases of EH with atypia, 91.66% (11/12) were MMR deficient (MMRd), whereas in EH without atypia 69.23% (32/46) were of MMRd. Paired expression of MLH1/PMS2 and MSH2/MSH6 was observed in EC whereas it was not seen in EH. MLH1 loss was the most common protein loss both in EC and EH with atypia. Conclusion MLH1/PMS2 combination was the most common protein deficiency seen in EC. We found considerable proportion of EC cases with MMRd. This implies the need of incorporating routine MMR protein assessment by immunohistochemistry in all the patients diagnosed as EC as it will affect the further treatment and management.