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

BACKGROUND. The frequency of synchronous or metachronous multiple primary c arcinomas in patients with endometrial carcinoma has been reported to be be tween 10% and 23% and is highest among all gynecologic carcinomas. However, clinical characteristics and underlying genetic abnormalities in endometri al carcinoma with multiple primary carcinomas has not been well clarified. Endometrial carcinoma is the most commonly associated extracolonic malignan cy in hereditary nonpolyposis colorectal carcinoma in which germ line mutat ions in DNA mismatch repair genes, particularly in MSH2 and MLH1, are known to cause this syndrome. The purpose of the current study was to investigat e clinicopathologic and familial characteristics including MSH2, MLH1, and p53 expression in endometrial carcinoma with multiple primary carcinomas, b y comparing them to endometrial carcinoma without other primary malignancie s. METHODS. Patients were divided into two groups: 30 patients with synchronou s or metachronous multiple primary carcinomas other than endometrial carcin oma and 116 patients with endometrial carcinoma without other primary malig nancies. Clinicopathologic characteristics, family history of cancer, and i mmunohistochemical protein expression of MSH2, MLH1, and p53 expression wer e investigated in both soups, and 15 endometria from benign disease were us ed for normal controls in immunohistochemistry. RESULTS. The frequency of high risk clinicopathologic factors of endometria l carcinoma and 5-year survival rates and the frequency of p53 overexpressi on were not statistically different between the two groups. However, the lo ss 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 thos e in which the patient had a family history of cancer, the frequency of thi s loss was especially high (11 of 13 and LO of 11, respectively). CONCLUSIONS. The clinical or biologic nature of endometrial carcinoma with multiple primary carcinomas seems to be similar to endometrial carcinoma al one. A high incidence of defective MSH2 and MLH1 protein in endometrial car cinoma with multiple primary carcinomas, however, suggests that abnormaliti es in the function of MSH2 and MLH1 may play an important role in tumorigen esis for patients with endometrial carcinoma with multiple primary carcinom as and their families. Cancer 2001;91:2056-64. (C) 2001 American Cancer Soc iety.