Genetic Instability and Inactivation of Mismatch Repair Proteins in Synchronous Multiple Colorectal Cancers

Abstract

To find fresh mutations in HNPCC cases, synchronous multiple colorectal cancers were examined. We selected thirty-one lesions in 19 cases of synchronous multiple colorectal cancers. Findings of MSI-High were detected in 6 of the 19 cases （31.6％）and 11 of the 31 lesions（35.5％）. The MSI-positive findings（MSI-H or MSI-L） were detected in 16 of the 19 cases（84.2％） and 26 of the 31 lesions（83.9％）. Fifteen of the 31 lesions（48.4％）showed negative stainings for MLH1 and/or MSH2 antigen, using immunhistochemical methods. Nine of the 11 lesions（81.8％）indeed showed negative immunostaining for MLH1 and/or MSH2 antigen. The results of the MSI status and expression of MLH1 and MSH2 agreed between different plural tumors in the same case. Moreover, the correlation between MSI-High and inactivation of MLH1 and MSH2 was recognized. These results suggest that MSI and immunohistochemical studies with antibodies of MLH1 and MSH2 are useful methods to find new HNPCC-patients who are not consistent with the criteria for HNPCC.