<b>MISMATCH REPAIR PROTEIN DEFICIENCY IN TRIPLE-NEGATIVE BREAST CARCINOMA</b>

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast carcinoma characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Due to limited targeted therapeutic options, there is growing interest in identifying molecular biomarkers that may guide treatment strategies. Deficiency of the DNA mismatch repair (MMR) system has emerged as a potential predictor of response to immunotherapy in several malignancies, but its prevalence and clinicopathological significance in TNBC remain uncertain. Objective: To determine the frequency and pattern of mismatch repair protein deficiency in triple-negative breast carcinoma and evaluate its association with clinicopathological characteristics. Methods: This retrospective cohort study was conducted at a tertiary care hospital and included 150 histologically confirmed TNBC cases diagnosed between January 2018 and December 2023. Immunohistochemistry was performed to evaluate expression of the four canonical MMR proteins (MLH1, PMS2, MSH2, and MSH6). Cases showing complete loss of nuclear staining of any protein with preserved internal controls were classified as MMR-deficient. Clinicopathological variables were collected from medical records and analyzed using appropriate statistical tests. A subgroup of cases underwent microsatellite instability testing by polymerase chain reaction for validation. Results: Among 150 TNBC cases, 10 tumors (6.7%) demonstrated mismatch repair deficiency, while 140 cases (93.3%) retained intact MMR protein expression. The most common pattern of protein loss involved PMS2, either alone or in combination with MLH1. No statistically significant associations were observed between MMR status and clinicopathological variables, including patient age, tumor grade, lymph node involvement, or PD-L1 expression. Microsatellite instability testing performed in a subset of cases showed concordance with immunohistochemical findings. Conclusion: Mismatch repair protein deficiency was identified in a small subset of triple-negative breast carcinoma cases. Although relatively uncommon, its detection may have potential clinical relevance for molecular characterization and therapeutic decision-making, particularly in the context of emerging immunotherapy strategies.