Cai Q, Sun M, Lu H, Zhang T, Mo S, Xu Y, Cai S, Zhu X, Shi D
Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.
Zhonghua Bing Li Xue Za Zhi. 2001 Oct;30(5):339-44.
To investigate the clinicopathological and molecular genetic characteristics of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees.
Four Chinese HNPCC pedigrees were studied using microdissection, microsatellite instability analysis, immunohistochemistry staining and direct DNA sequencing for hMSH2 and hMLH1 genes.
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.
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.
探讨中国遗传性非息肉病性结直肠癌（HNPCC）家系的临床病理及分子遗传学特征。
采用显微切割、微卫星不稳定性分析、免疫组织化学染色及hMSH2和hMLH1基因直接DNA测序等方法对4个中国HNPCC家系进行研究。
4名先证者的所有5份肿瘤组织在2个以上位点均显示高水平微卫星不稳定性（RER + 表型）。4例中有3例hMSH2蛋白表达缺失，1例无hMLH1蛋白表达。鉴定出3个病理性种系突变（hMSH2上2个，hMLH1上1个）。
中国典型HNPCC家系错配修复基因种系突变相对常见。微卫星不稳定性分析和免疫组织化学染色可能是直接DNA测序检测错配修复基因前的有效筛查方法。有必要建立更适合中国HNPCC家系的临床标准和分子诊断策略。
