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Mucinous carcinomas of the colon and rectum show higher rates of microsatellite instability and lower rates of chromosomal instability
Author(s) -
Kazama Yoshihiro,
Watanabe Toshiaki,
Kanazawa Takamitsu,
Tada Tomohiro,
Tanaka Junichiro,
Nagawa Hirokazu
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21022
Subject(s) - microsatellite instability , loss of heterozygosity , rectum , methylation , epigenetics , cancer research , dna methylation , pathology , medicine , biology , microsatellite , gene , gene expression , genetics , allele
BACKGROUND The clinicopathologic significance of mucinous carcinomas (Muc) of the colon and rectum has been widely discussed, but there have been few studies on Muc regarding genetic and epigenetic alterations. The current study analyzed genetic and epigenetic alterations of Muc to clarify their differences from well differentiated adenocarcinomas (WD). METHODS Thirty‐nine cases of Muc and 39 cases of WD were investigated. Cases of WD were matched with cases of Muc for T classification and tumor location. Microsatellite instability (MSI) status and loss of heterozygosity (LOH) of four loci (2p, 5q, 17p, 18q) were evaluated. The methylation status of the hMLH1 promoter region in Muc was also examined. RESULTS “MSI tumors” were defined as those that showed MSI‐high, and “chromosomal instability (CIN) tumors” were defined as those that showed LOH but not MSI‐high. MSI tumors were significantly more frequent in Muc (30.8%) than in WD (5.1%). CIN tumors were significantly less frequent in Muc (53.8%) than in WD (87.2%). In Muc, MSI tumors were significantly more frequent in the proximal colon (55.6%) than in the distal colon (9.5%). Also, methylation of the hMLH1 promoter region in Muc was significantly more frequent in MSI tumors (83.3%) than in CIN tumors (27.8%) ( P = 0.0077). CONCLUSIONS When matched for T classification and tumor location, Muc shows higher rates of MSI and lower rates of CIN than WD.. Muc shows different characteristics according to tumor location, and methylation of the hMLH1 promoter region strongly correlates with Muc tumors showing MSI. Cancer 2005. © 2005 American Cancer Society.