Chromosomally and microsatellite stable colorectal carcinomas without the CpG island methylator phenotype in a molecular classification
Chromosomally and microsatellite stable colorectal carcinomas without the CpG island methylator phenotype in a molecular classification
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DOI：
10.3892/ijo_00000343
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发表时间：
2009-08-01
影响因子：
5.2
通讯作者：
Prall, Friedrich
中科院分区：
文献类型：
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作者：
Ostwald, Christiane;Linnebacher, Michael;Prall, Friedrich
我们假设，在对结直肠癌（CRC）的综合分析中，目前已知的三种主要的致癌分子机制（即，染色体不稳定性、微卫星不稳定性和CpG岛甲基化表型（CIMP）将与指示这些途径的分子特征相关，从而允许分子分类。对前瞻性收集的130例临床病理学特征良好的CRC进行了染色体不稳定性（DNA流式细胞术和微卫星标记5 q21、8 p21、9 q21、17 p13和18 q21的等位基因不平衡分析）、微卫星不稳定性（Bethesda panel）、CIMP（MethyLight）和K-ras、B-raf、APC和p53突变检测。形态学进行了审查，并通过免疫组织化学评估核B-连环蛋白易位。根据分子特征，可以划分为散发性高度微卫星不稳定肿瘤、遗传性非息肉病性结肠癌综合征肿瘤和“散发性标准型”CRC（分别为14、4和55）。然而，在其余46例肿瘤中观察到类别之间的重叠，其中观察到广泛或偶尔的甲基化（不包括MLH 1），并且大多数具有染色体不稳定性。重要的是，观察到一组11个肿瘤没有微卫星或染色体不稳定性，也没有任何甲基化。在形态学上，这些肿瘤没有任何区别特征，所有肿瘤都有肿瘤出芽，10个显示核B-连环蛋白易位。总体而言，这些数据提供了CRC中的分子类别的概述，这些分子类别应在癌变研究和临床病理学研究中考虑。具体来说，在8.46%的肿瘤中没有CIN，MSI和CIMP，这是一个需要注意的群体。
We hypothesized that in a comprehensive analysis of colorectal carcinomas (CRC) the three currently known major molecular mechanisms of carcinogenesis (i.e., chromosomal instability, microsatellite instability, and CpG island methylator phenotype, CIMP) would associate with the molecular features indicative of these pathways, allowing a molecular classification. A prospectively collected clinicopathologically well-characterized series of 130 CRCs was tested for chromosomal instability (DNA-flow cytometry and analysis of allelic imbalance with microsatellite markers 5q21, 8p21, 9q21, 17p13, and 18q21), microsatellite instability (Bethesda panel), CIMP (MethyLight), and mutations of K-ras, B-raf, APC, and p53. Morphology was reviewed, and nuclear B-catenin translocation was assessed by immunohistochemistry. Based on the molecular features, sporadic high-degree microsatellite instable tumours, tumours of the hereditary non-polyposis coli carcinoma syndrome, and 'sporadic standard-type' CRC could be delineated (14, 4, and 55, respectively). However, overlap between classes was seen for 46 of the remaining tumours where widespread or occasional methylations (excluding MLH1) were observed, and the majority had chromosomal instability. Importantly, a group of 11 tumours was observed without either microsatellite or chromosomal instability, nor any methylation. Morphologically, these tumours were without any distinguishing features, all had tumour budding and 10 showed nuclear B-catenin translocation. Overall, the data give an overview of the molecular classes in CRC that should be taken into account in studies on carcinogenesis and clinicopathological studies. Specifically, the absence of CIN, MSI, and CIMP in an 8.46% fraction of tumours delineates a group to be aware of.