Poorly differentiated colorectal adenocarcinomas show higher rates of microsatellite instability and promoter methylation of p16 and hMLH1: a study matched for T classification and tumor location.
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.
Kazama
Yoshihiro
Y
Department of Surgical Oncology, the University of Tokyo, Bunkyo-ku, Tokyo, Japan. ykazama-tky@umin.ac.jp
Watanabe
Toshiaki
T
Kanazawa
Takamitsu
T
Tanaka
Junichiro
J
Tanaka
Toshiaki
T
Nagawa
Hirokazu
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1