Microsatellite instability and hMLH1/hMSH2 expression in young endometrialcarcinoma patients: Associations with family history and histopathology

Endometrial cancer is the second most common malignancy in patients with he reditary nonpolyposis colorectal cancer (HNPCC), The age at diagnosis of HN PCC-associated endometrial cancer is approximately 15 years younger than fo r sporadic endometrial cancer. Our current study was undertaken to determin e the frequency of microsatellite instability (MSI) and absence of hMLH1 or hMSH2 protein expression in young patients with endometrial carcinoma and to correlate these findings with histopathologic and clinical features. End ometrial carcinoma from 62 women (23-52 years, median age 46) were assessed for MSI, Twenty-one of the 62 (34%) tumors demonstrated MSI, Of the 21 tum ors demonstrating MSI, 12 showed an absence of hMLH1 expression, 4 showed a n absence of hMSH2 expression, and 5 demonstrated normal expression of both proteins. All 41 tumors without MSI demonstrated normal hMLH1 and hMSH2 ex pression. Two patients with MSI tumors fulfilled the Amsterdam criteria for HNPCC, while 2 had histories suggestive of HNPCC, None of the patients wit h tumors without MSI had a personal or family cancer history suggestive of HNPCC, The MSI phenotype was associated (P < 0.05) with high FIGO stage and grade, cribriform growth pattern, mucinous differentiation and necrosis. O ur findings suggest that the frequency of HNPCC in young endometrial cancer patients is relatively low when compared with the frequency of HNPCC in yo ung colorectal cancer patients. Defects of the MMR proteins hMSH2 or hMLH1 account for MSI in most but not all endometrial cancers from young patients . Int. J, Cancer 86: 60-66, 2000. (C) 2000 Wiley-Liss, Inc.