Objective: Many familial and sporadic endometrial carcinomas have microsatellite instability (MSI) due to mutations in the DNA mismatch repair (MMR) genes. Immunohistochemistry (IHC) for MMR proteins is used to detect MSI in endometrial carcinomas (ECs) and to screen patients for Lynch syndrome (LS). The present study was conducted to evaluate MMR protein expression by using IHC in ECs and to determine the association of MSI-related EC with various clinicopathologic parameters. Materials and Methods: This was a retrospective study of 83 cases of primary EC. IHC was performed using tissue microarrays for MMR proteins. Loss of expression of these proteins was correlated with various clinicopathologic features. Results: Loss of expression of at least one of the MMR proteins was seen in 62.7% cases. Loss of PMS2 (54.2%) expression was most frequent, followed by MLH1 (49.4%) and MSH2 (31.3%). Of the patients age <50 (n = 25), 76% had loss of MMR expression. Loss of MSH6 expression alone as well as in combination with MSH2, was significantly more frequent among these younger patients, compared to older ones (p = 0.03). Loss of expression was significantly (p < 0.001) more frequent (78.8%) in low-grade endometrioid carcinomas. Conclusions: The present study showed loss of MMR expression in 62.7% ECs. Lower tumor grade was the most significant predictor of MMR loss. A proportion of these cases might be associated with LS. Screening these patients for MMR deficiency and subsequent confirmation by mutation testing is essential for early identification of such cases.

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