The association of mismatch repair deficiency with histopathological parameters in endometrial carcinoma: A study from the kurdistan region of Iraq.

BACKGROUND: Microsatellite instability (MSI) is one of the four molecular classes of endometrial carcinomas (EC) identified by The Cancer Genome Atlas (TCGA), which is associated with an intermediate prognosis. The identification of mismatch deficient (MMRd) tumors has become essential for clinical decision-making and therapeutic management. OBJECTIVES: To analyze mismatch repair (MMR) protein expression by immunohistochemistry (IHC) and determine its association with the clinicopathological characteristics of EC, highlighting its potential role as a prognostic factor in clinical practice. MATERIALS AND METHODS: The retrospective observational study was conducted from 100 patient specimens with EC after hysterectomy or dilatation and curettage (D&C), from January 2017 to December 2024 at Hiwa Hematology/Oncology Hospital. Patients' age, surgical type, clinicopathological information, and histopathological characteristics were obtained from the hospital database. Then, the expression of MMR proteins (PMS2, MLH1, MSH2, and MSH6) was assessed in specimens using IHC on formalin-fixed paraffin blocks. Finally, the expression of MMR proteins in relation to clinicopathological parameters was determined. RESULTS: Abnormal expression of MMR proteins was detected in 22 cases, of which 18 showed combined loss of MLH1/PMS2 expression, 3 showed combined loss of MSH2/MSH6, while only one case revealed isolated loss of PMS2. CONCLUSION: MMRd with predominance of an MLH1/PMS2 loss pattern is significantly linked to endometrioid histological type, tumor grading, and tumor-infiltrating lymphocytes. MMRd serves as a useful molecular biomarker and potential predictor of the immune microenvironment, supporting its role in prognosis and personalized therapy.