Cai Q, Sun M H, Lu H F, Zhang T M, Mo S J, Xu Y, Cai S J, Zhu X Z, Shi D R
Department of Pathology, Cancer Hospital/Cancer Institute, Fudan University, Shanghai 200032, China.
World J Gastroenterol. 2001 Dec;7(6):805-10. doi: 10.3748/wjg.v7.i6.805.
To study the clinicopathological and molecular genetic characteristics of typical Chinese hereditary nonpolyposis cotorectal cancer (HNPCC) families.
Four typical Chinese HNPCC families were analyzed using microdissection, microsatellite instability analysis, immunostaining of hMSH2 and hMLH1 proteins and direct DNA sequencing of hMSH2 and hMLH1 genes.
All five tumor tissues of 4 probands from the 4 typical Chinese HNPCC families showed microsatellite instability at more than two loci (MSI-H or RER+ phenotype). Three out of the 4 cases lost hMSH2 protein expression and the other case showed no hMLH1 protein expression. Three pathological germline mutations (2 in hMSH2 and 1 in hMLH1), which had not been reported previously, were identified. The same mutations were also found in other affected members of two HNPCC families,respectively.
Typical Chinese HNPCC families showed relatively frequent germline mutation of mismatch repair genes. High-level microsatellite instability and loss of expression of mismatch repair genes correlated closely with germline mutation of mismatch repair genes. Microsatellite instability analysis and immunostaining of mismatch repair gene might serve as effective screening methods before direct DNA sequencing. It is necessary to establish clinical criteria and molecular diagnostic strategies more suitable for Chinese HNPCC families.
研究典型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、hMSH2和hMLH1蛋白免疫染色以及hMSH2和hMLH1基因直接DNA测序对4个典型中国HNPCC家系进行分析。
4个典型中国HNPCC家系的4名先证者的所有5个肿瘤组织在两个以上位点显示微卫星不稳定性（MSI-H或RER+表型）。4例中有3例hMSH2蛋白表达缺失，另1例无hMLH1蛋白表达。鉴定出3个病理性种系突变（hMSH2中2个，hMLH1中1个），此前未见报道。在两个HNPCC家系的其他患病成员中也分别发现了相同的突变。
典型中国HNPCC家系错配修复基因种系突变相对常见。高水平微卫星不稳定性和错配修复基因表达缺失与错配修复基因种系突变密切相关。微卫星不稳定性分析和错配修复基因免疫染色可作为直接DNA测序前的有效筛查方法。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。
