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

Abstract

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