AIM:To study the clinicopathological and molecular geneticcharacteristics of typical Chinese hereditary nonpolyposiscotorectal cancer(HNPCC)families.METHODS:Four typical Chinese HNPCC families wereanalyzed using microdissection,microsatellite instabilityanalysis,immunostaining of hMSH2 and hMLH1 proteinsand direct DNA sequencing of hMSH2 and hMLH1 genes.RESULTS:All five tumor tissues of 4 probands from the 4typical Chinese HNPCC families showed microestelliteinstability at more than two loci(MSI-H or RER+phenotype).Three out of the 4 cases lost hMSH2 proteinexpression and the other case showed no hMLH1 proteinexpression.Three pathological germline mutations(2 inhMSH2 and 1 in hMLH1),which had not been reportedprevlously,were identified.The same mutations were alsofound in other affected members of two HNPCC families,respectively.CONCLUSION:Typical Chinese HNPCC families showedrelatively frequent germline mutation of mismatch repairgenes.High-level mlcrosatellite inatability and loss ofexpression of mismatch repair genes correlated closely withgermlina mutation of mismatch repair genes.Microsatelliteinatabllity analysis and immunoataining of mismatch repairgens might serve as effective screening methods beforedirect DNA sequencing.It is necessary to establish clinicalcriteria and molecular diagnostic strategies more suitable forChinese HNPCC families. AIM:To study the clinicopathological and molecular geneticcharacteristics of typical Chinese hereditary nonpolyposiscotorectal cancer (HNPCC)families.METHODS:Four typical Chinese HNPCC families wereanalyzed using microdissection,microsatellite instability analysis,immunostaining of hMSH2 and hMLH1 proteinsand direct DNA sequencing of hMSH2 and hMLH1 genes.RESULTS :All five tumor tissues of 4 probands from the 4typical Chinese HNPCC families demonstrated microestelliteinability at more than two loci(MSI-H or RER+phenotype).Three out of the four cases lost hMSH2 proteinexpression and the other case showed no hMLH1 proteinexpression.Three Pathological germline mutations(2 inhMSH2 and 1 in hMLH1), which had not been reportedprevlously,were identified.The same mutations were also found in other affected members of two HNPCC families,respectively.CONCLUSION:Typical Chinese HNPCC ed pathrangingly frequent germline mutation of mismatch repairgenes .High-level mlcrosatellite inatability and loss of Expression of mismatch repair tools correlated closely with germina mutation of mismatch repair genes.Microsatelliteinatabllity analysis and immunoataining of mismatch repairgens might serve as effective screening methods before direct DNA sequencing.It is necessary to peace clinicalcriteria and molecular diagnostic strategies more suitable forChinese HNPCC families.