EVALUATION OF IMMUNOHISTOCHEMICAL EXPRESSION OF MISMATCH REPAIR PROTEINS IN ENDOMETRIAL CARCINOMA AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS IN A SAMPLE OF IRAQI PATIENTS (A CLINICOPATHOLOGICAL STUDY)

Background: Carcinoma of the endometrium is the most common gynecologic malignancy, and its increasing prevalence is attributed to various risk factors, including obesity, hypertension, and diabetes. Endometrial cancer is more frequently categorized by molecular subgroups based on mutation burden and copy number alterations rather than histological findings. Recent advancements in genomic analysis have uncovered that approximately 20–30% of endometrial cancer cases exhibit a mismatch repair deficiency phenotype. It serves as a molecular classification a companion diagnostic for immunotherapy, and a secondary screening for Lynch syndrome. Aim of study: To evaluate the expression of mismatch repair proteins on endometrial adenocarcinoma in a sample of Iraqi female patients and to correlate its expression with different clinic-pathological findings. Patient and methods: A retrospective study was carried out at Al-Yarmouk Teaching Hospital and private lab in Baghdad (from January 2024 to January 2025). It included fifty formalin- fixed, paraffin embedded tissue blocks of endometrial carcinoma female patients were included in this study. Five sections of 5μm thickness were acquired from each block. One of them was stained with hematoxylin and eosin stain (H and E) for histopathological revision, the other sections were stained immunohistochemically for MMR proteins expression (PMS2, MLH1, MSH2, MSH6), which was done in private lab in Baghdad in August 2024. Results: In this study, the most common histological type was endometrioid (84%). We noticed that 24% of patients showed negative PMS2 expression; 14% showed negative MLH1 expression; 20% showed negative MSH2 expression; and 20% showed negative MSH6 expression. Mismatch repair protein expression showed that 32% of patients had deficient mismatch repair protein expression. Deficient mismatch repair protein expression was significantly associated with younger age patients, positive family history; endometroid histology type; FIGO stage IA, FIGO grade I; and TNM stage T1A. Positive expressions of any protein were significantly associated with positive expressions of other proteins. Conclusion: Endometrial carcinomas occur mainly in postmenopausal women. The percentage of immunohistochemical expression of microsatellite instability in endometrial carcinoma in Iraqi females are like the results of other studies worldwide. Endometroid type of endometrial carcinoma is the most common type, and it is most associated with microsatellite instability. Mismatch repair proteins evaluation by immunohistochemistry is simple and affordable method for assessing microsatellite instability that is useful in the prognosis and treatment of endometrial carcinoma.