Germline mutation analysis, microsatellite instability and clinical pathology in Hazakh in China hereditary nonpolyposis colorectal cancer pedigree

Abstract

Objective To study the significance of mismatch repair (MMR) gene and microsatellite instability (MSI) in Hazakh in China hereditary nonpolyposis colorectal cancer (HNPCC) pedigree.Methods The tumor tissues and normal intestine mucosa of the 105 members of this family were immunohistochemically examined for hMLH1 and hMSH2.The mutation of BAT25,BAT26,D2S123,D5S346 and D17S250 were analyzed with polymerase chain reaction-single-stmded conformation polymorphism (PCR-SSCP) in tissue paraffin imbedding in all cases of the family.Results MSI-positive rate of 17tumor in HNPCC families group was 100 ％,in which there are 16 patients (94.1％) with high frequency microsatellite instability (MSI-H),1 patients with low frequency microsatellite instability (MSI-L)(5.9％).The negative expression of hMLH1 or hMSH2 rate of 17 tumor in HNPCC families group was 100％.There are 44 patients (50.0％) in the other 88 members of the HNPCC family with MSI-H.There are 40 patients with hMLH1 or hMSH2 MMR protein expression absence in the 44 patients with MSI-H.Conclusion HNPCC patients with MSI-H and hMLH1 or hMSH2 MMR protein expression absence have a better consistency with earlier age of onset,right colon cancer incidence and the occurrence of poorly differentiated carcinoma. Key words: Hereditary nonpolyposis colorectal cancer; Microsatellite instability; Mismatch repair gene; Hazakh