遗传性非息肉病性大肠癌微卫星不稳定临床病理和错配修复基因变异的研究  

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

作　　者：张剑权[1,2] 符国珍[2] 吴海红[2] 吕明[2] 黄桂林[1] 周帅[2] 

机构地区：[1]石河子大学医学院第一附属医院胃肠外,新疆832008 [2]中南大学湘雅医学院附属海口医院肝胆外科

出　　处：《中华实验外科杂志》2014年第2期245-247,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81060035）

摘　　要：目的 检测新疆哈萨克遗传性非息肉病性大肠癌（HNPCC）大家系微卫星不稳定和错配修复基因表达,探讨两者的关系及对HNPCC家系检测的意义.方法 以调查随访完整的哈萨克HNPCC大家系105例成员为研究对象,采用免疫组织化学技术,检测所有成员大肠组织中hMLH1、hMSH2蛋白表达.从石蜡包埋组织中提取DNA,选择BAT25、BAT26、D2S123、D5S346和D17S250 5个微卫星位点行聚合酶链反应（PCR）.结果 HNPCC家系的17例肿瘤患者中MSI的阳性率为100％,其中高度微卫星不稳定（MSI-H）的患者16例（94.1％）;低度微卫星不稳定（MSI-L）的患者1例（5.9％）;这17例患者均存在hMLH1或hMSH2表达阴性.家系88例未发病成员MSI-H者44例（50.0％）,这44例成员中有40例hMLH1或hMSH2表达阴性.结论 HNPCC患者中MSI-H的患者与错配修复基因hMLH1及hMSH2表达缺失、较早的发病年龄、右半结肠癌的发生率及低分化癌的发生之间有较好的一致性.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.

关 键 词：遗传性非息肉病性大肠癌 微卫星不稳定 错配修复基因 哈萨克族 

分 类 号：R735.34[医药卫生—肿瘤]