EXPRESSION OF HMSH2 AND HMLH1 IN COLORECTAL CARCINOMAS WITH MICROSATELLITE INSTABILITY

Microsatellite instability (MIN) due to defective mismatch repair (MMR ) genes has been reported in a subset of sporadic colorectal carcinoma s and in the majority of tumors from patients with hereditary nonpolyp osis colorectal cancer (HNPCC) syndrome. Among the known MMR genes, hM SH2 and hMLH1 genes are known to be predominantly altered in HNPCC pat ients and MIN-positive tumors. In this study, we examined MIN and the protein expression pattern of the hMSH2 and hMLH1 by Western blot and immunohistochemistry from 32 sporadic colorectal carcinomas. MIN was o bserved in 6 (18%) colorectal carcinomas. Of the 6 MIN-positive tumors , one case showed no expression of either protein, 3 cases showed an a bsence of hMSH2 protein expression, one case showed an absence of hMLH 1 protein expression and one case showed no altered expression of eith er protein by immunohistochemistry. The decreased expression of the hM SH2 protein in a tumor compared to the normal mucosa was also observed in 5 of the 6 MIN-positive cases by Western blot analysis. All of the MIN-negative tumors showed expression of both proteins by immunohisto chemistry. Thus most of the MIN-positive tumors appear to be directely related to the altered expression of these two genes and can be diagn osed by the examination of protein expression.