Exploring Microsatellite Instability in Endometrial Carcinomas: Clinicopathological Correlations and Clinical...

Endometrial cancer is the second most diagnosed gynecologic malignancy among women worldwide. The recent understanding of molecular classification of endometrial carcinoma have become important aspect of patient directed treatment. The importance of Microsatellite Instability (MSI) has been highlighted in the molecular classification emphasizing that patients belonging to MSI subgroup differ from other subgroups for molecular abnormalities, hereditary risk factors, prognosis, and response to treatment. This study was therefore conducted to investigate the frequency of MSI in endometrial carcinomas and its association with clinicopathological parameters. Total of 109 cases were enrolled in the study over a duration of 3 years. Patients' demographic data was recorded from requisition forms. Cases were examined in routine Hematoxylin and Eosin (HE) sections. Tumor infiltrating Lymphocytes (TIL) were assessed manually by criteria proposed by International Immunooncology Biomarkers Working Group. One representative paraffin block having sufficient number of viable tumor cells was selected for immunohistochemistry (IHC) staining for mismatch repair (MMR) proteins (MLH1, MSH2, MSH2 and MSH6). Out of toal 109 cases, 100 were endometrioid, 5 were serous carcinoma, 2 were clear cell and 2 were carcinosarcoma. Seventy-seven cases (71%) were proficient mismatch repair (pMMR) and thirty two (29.00%) cases were deficient mismatch repair (dMMR). MMR deficiency was seen only in endometrioid carcinomas. No association was seen with age, size, site, myometrial invasion, tumor grade, lympho-vascular invasion (LVI) and stage of the tumor. There was higher trend towards more frequent lymph node involvement. Strong association was seen with high TIL. MSI testing which has been used historically to identify patients with Lynch Syndrome and evaluate the severity and prognosis of MSI carcinomas now plays an important role in identifying patients who will benefit from targetable therapy. MMR study therefore recommended in all cases of endometrial carcinomas and detection of MMR proteins by IHC can indirectly reflect the status of MSI and is a reliable method of MSI detection.