Lamberti C, Mangold E, Pagenstecher C, Jungck M, Schwering D, Bollmann M, Vogel J, Kindermann D, Nikorowitsch R, Friedrichs N, Schneider B, Houshdaran F, Schmidt-Wolf I G H, Friedl W, Propping P, Sauerbruch T, Büttner R, Mathiak M
Department of Internal Medicine I,University of Bonn, Bonn, Germany.
Digestion. 2006;74(1):58-67. doi: 10.1159/000096868. Epub 2006 Mar 3.
Hereditary non-polyposis colorectal cancer (HNPCC) is a major form of familial colorectal cancer (CRC). It is diagnosed when either the Amsterdam criteria (AC) are fulfilled or mutations in one of the mismatch repair (MMR) genes have been identified. This project aims at estimating the proportion of HNPCC among unselected patients with CRC.
During a period of 2 years, a total of 351 non-selected patients with CRC were registered prospectively. 92 patients met the Bethesda criteria (9 of them fulfilled the AC) and 259 did not. 348 tumours were examined for microsatellite instability (MSI) and expression of MMR proteins.
MSI-H and MSI-L were identified in 17 and 6%, respectively. Loss of MSH2 or MLH1 was found in 1.5 and 8.8%, respectively. Based on the results of tumour tissue analyses, 80 patients with MSI and/or loss of MSH2 or MLH1 expression were identified as candidates for germline mutation screening. DNA of 40/80 patients was available. These patients were screened for MSH2 and MLH1 mutations; 19/40 patients with MSI and normal MSH2 or MLH1 expression were screened for mutations in MSH6. Three patients had relevant MMR gene mutations and six variants of unknown functional relevance were detected.
After adjusting for the cases not evaluable for germline mutations, 1.7% of the CRC patients had HNPCC proven by molecular genetics.
遗传性非息肉病性结直肠癌（HNPCC）是家族性结直肠癌（CRC）的一种主要形式。当满足阿姆斯特丹标准（AC）或已鉴定出错配修复（MMR）基因之一发生突变时，即可诊断该病。本项目旨在估计未经选择的CRC患者中HNPCC的比例。
在2年期间，前瞻性登记了总共351例未经选择的CRC患者。92例患者符合贝塞斯达标准（其中9例满足AC），259例不符合。对348个肿瘤进行了微卫星不稳定性（MSI）和MMR蛋白表达检测。
分别在17%和6%的肿瘤中鉴定出微卫星高度不稳定（MSI-H）和微卫星低度不稳定（MSI-L）。分别在1.5%和8.8%的肿瘤中发现了MSH2或MLH1缺失。根据肿瘤组织分析结果，80例MSI和/或MSH2或MLH1表达缺失的患者被确定为种系突变筛查的候选对象。40/80例患者的DNA可用。对这些患者进行了MSH2和MLH1突变筛查；对19/40例MSI且MSH2或MLH1表达正常的患者进行了MSH6突变筛查。3例患者有相关的MMR基因突变，检测到6个功能相关性未知的变异。
在对无法进行种系突变评估的病例进行校正后，1.7%的CRC患者经分子遗传学证实患有HNPCC。
