Clinicopathologic and familial characteristics of endometrial carcinoma with multiple primary carcinomas in relation to the loss of protein expression of MSH2 and MLH1.

Abstract

The frequency of synchronous or metachronous multiple primary carcinomas in patients with endometrial carcinoma has been reported to be between 10% and 23% and is highest among all gynecologic carcinomas. However, clinical characteristics and underlying genetic abnormalities in endometrial carcinoma with multiple primary carcinomas has not been well clarified. Endometrial carcinoma is the most commonly associated extracolonic malignancy in hereditary nonpolyposis colorectal carcinoma in which germ line mutations in DNA mismatch repair genes, particularly in MSH2 and MLH1, are known to cause this syndrome. The purpose of the current study was to investigate clinicopathologic and familial characteristics including MSH2, MLH1, and p53 expression in endometrial carcinoma with multiple primary carcinomas, by comparing them to endometrial carcinoma without other primary malignancies. Patients were divided into two groups: 30 patients with synchronous or metachronous multiple primary carcinomas other than endometrial carcinoma and 116 patients with endometrial carcinoma without other primary malignancies. Clinicopathologic characteristics, family history of cancer, and immunohistochemical protein expression of MSH2, MLH1, and p53 expression were investigated in both groups, and 15 endometria from benign disease were used for normal controls in immunohistochemistry. The frequency of high risk clinicopathologic factors of endometrial carcinoma and 5-year survival rates and the frequency of p53 overexpression were not statistically different between the two groups. However, the loss of MSH2 and/or MLH1 expression was significant in endometrial carcinoma with multiple primary carcinomas, when compared with endometrial carcinoma alone (22 of 30 vs. 31 of 116). In cases with multiple primary carcinomas, particularly those diagnosed before the patient was 55 years of age or those in which the patient had a family history of cancer, the frequency of this loss was especially high (11 of 13 and 10 of 11, respectively). The clinical or biologic nature of endometrial carcinoma with multiple primary carcinomas seems to be similar to endometrial carcinoma alone. A high incidence of defective MSH2 and MLH1 protein in endometrial carcinoma with multiple primary carcinomas, however, suggests that abnormalities in the function of MSH2 and MLH1 may play an important role in tumorigenesis for patients with endometrial carcinoma with multiple primary carcinomas and their families.