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Objective: We aimed to investigate the frequency of microsatellite instability (MSI) in endometrial carcinoma in our population and its association with clinico-pathologic features. Methods: A total of 126 cases of primary endometrial carcinoma were included in the study that underwent surgical resections. All slides of these cases were reviewed and representative paraffin fixed tissue blocks were selected for MLH1, MSH2, MSH6 and PMS2 IHC staining. IHC expression was categorized into five groups: no loss of expression; loss of expression of all four antibodies; combined loss of MLH1/PMS2; combined loss of MSH2/MSH6; and isolated loss of MLH1. Pathological records of all cases were retrieved from patient files. Result: Abnormal expression of MSI was noted in 56 cases (44.4%) among which 16 cases showed loss of nuclear expression of all markers, 34 cases showed loss of MLH1/PMS2 expression, 4 cases showed loss of MSH2/MSH6 while only 2 cases revealed isolated loss of MLH. Personal and family history suggestive of inherited cancer susceptibility was revealed in 11 cases most of which were associated with MSH2/MSH6 loss. Significant association of MSI expression was found with tumor stage and personal/family history of endometrial/ colon cancer. Conclusion: A high frequency of endometrioid cancers in our study showed abnormal expression of MSI markers, most of which depicted MLH1/PMS2 loss and were not associated with inherited cancer susceptibility. On the other hand, a minority of cases showed loss of all MSI markers or MSH2/MSH6 loss and were significantly associated with family/personal history of cancer. Therefore, we suggest that epigenetic changes in MLH1 locus may be a predominant pathway of tumorigenesis in our population rather than inherited mutation of MSI genes; however more large scale studies with genetic testing are required to validate this observation.

Microsatellite Instability in Endometrial Carcinoma by Immunohistochemistry, Association with Clinical and Histopathologic Parameters