OBJECTIVE: To investigate the clinicopathological and molecular genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. METHODS: Four Chinese HNPCC pedigrees were studied using microdissection, microsatellite instability analysis, immunohistochemistry staining and direct DNA sequencing for hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues from 4 probands showed high level of microsatellite instability at more than 2 loci(RER + phenotype). Three of 4 cases lost hMSH2 protein expression and one case showed no hMLH1 protein expression. Three pathological germline mutations (2 on hMSH2 and 1 on hMLH1) were identified. CONCLUSIONS: Chinese typical HNPCC kindreds showed relatively frequent germline mutations of mismatch repair genes. Microsatellite instability analysis and immunohistochemistry staining might be the effective screening methods before direct DNA sequencing for the detection of mismatch repair genes. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC kindreds.
OBJECTIVE: To investigate the clinicopathological and molecular genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. METHODS: Four Chinese HNPCC pedigrees were studied using microdissection, microsatellite instability analysis, immunohistochemistry staining and direct DNA sequencing for hMSH2 and hMLH1 genes. RESULTS: All five tumor tissues from 4 probands showed high level of microsatellite instability at more than 2 loci(RER + phenotype). Three of 4 cases lost hMSH2 protein expression and one case showed no hMLH1 protein expression. Three pathological germline mutations (2 on hMSH2 and 1 on hMLH1) were identified. CONCLUSIONS: Chinese typical HNPCC kindreds showed relatively frequent germline mutations of mismatch repair genes. Microsatellite instability analysis and immunohistochemistry staining might be the effective screening methods before direct DNA sequencing for the detection of mismatch repair genes. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC kindreds.