Poorly Differentiated Colorectal Adenocarcinomas Show Higher Rates of Microsatellite Instability and Promoter Methylation ofp16andhMLH1:A Study Matched for T Classification and Tumor Location


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Abstract

Background:Extensive genetic and epigenetic analysis of poorly differentiated colorectal adenocarcinomas (Por) has been difficult, as the number of cases is too small.Methods:We investigated genetic and epigenetic alterations of 53 cases of Por and 53 cases of well-differentiated colorectal adenocarcinomas (WD) to clarify their differences. The cases of WD were matched with the cases of Por for T classification and tumor location, which influence genetic and epigenetic alterations. We evaluated microsatellite instability (MSI) status and loss of heterozygosity (LOH) of four loci (2p, 5q, 17p, 18q), and defined “MSI tumors” as those that showed MSI-H, and “chromosomal instability (CIN) tumors” as those that showed LOH but not MSI-H. Further, we evaluated the methylation status of the hMLH1 and p16 promoter region.Results:MSI tumors were significantly more frequent in Por (22.6%) than in WD (3.8%; P = 0.0041). CIN tumors were significantly less frequent in Por (64.2%) than in WD (83.0%; P = 0.046). Further, methylation of the p16 and hMLH1 promoter region was significantly more frequent in Por than in WD (P = 0.037, P = 0.047, respectively).Conclusions:Our results indicate that Por tumorigenesis strongly correlates with MSI and methylation of the p16 and hMLH1 promoter region.J. Surg. Oncol. 2008;97:278-283. © 2007 Wiley-Liss, Inc.

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