Tischoff I, Tannapfel A
Institut für Pathologie, Ruhr-Universität Bochum an der BG Universitätsklinik Bergmannsheil, Bochum.
Z Gastroenterol. 2008 Oct;46(10):1202-6. doi: 10.1055/s-2008-1027406. Epub 2008 Oct 20.
Colorectal carcinomas are the third most common malignant tumours worldwide with an incidence of 570,000 per year. According to their molecular mechanisms, sporadic colorectal carcinomas can be divided into two different phenotypes. The genetic phenotype, 50 to 70 % of all sporadic colorectal carcinomas, is characterised by a chromosomal instability (CIN) with the classical adenoma-carcinoma sequence due to alteration of the APC-betacatenin pathway with p53 mutations, SMAD alterations and LOH (loss of heterozygositiy) of 5q, 17 p 18q. On the other, the CpG island methylator phenotype (CIMP+) was described with an epigenetic inactivation of tumour suppressor genes that are typically inactivated by germline mutations in familiar cancer syndromes, e. g., Rb, VHL, hMLH1, p16 or BRCA. Colorectal carcinomas of the CIMP+ type often show a high microsatellite instability (MSI+) caused by aberrant promoter methylation of the missmatch repair gene hMLH1. Further CIMP+ are located in the proximal right-side colon and show a poor grading with mucinous or signet-cell differentiation.
结直肠癌是全球第三大常见恶性肿瘤，每年发病率为57万例。根据其分子机制，散发性结直肠癌可分为两种不同的表型。遗传表型占所有散发性结直肠癌的50%至70%，其特征是染色体不稳定（CIN），具有经典的腺瘤-癌序列，这是由于APC-β-连环蛋白途径改变，伴有p53突变、SMAD改变以及5q、17p、18q的杂合性缺失（LOH）。另一方面，CpG岛甲基化表型（CIMP+）的描述是，肿瘤抑制基因发生表观遗传失活，这些基因通常在家族性癌症综合征中因种系突变而失活，例如Rb、VHL、hMLH1、p16或BRCA。CIMP+型结直肠癌通常表现出高度微卫星不稳定（MSI+），这是由错配修复基因hMLH1的异常启动子甲基化引起的。此外，CIMP+肿瘤位于右半结肠近端，分级较差，伴有黏液或印戒细胞分化。
