Low frequency of promoter methylation of O6-methylguanine DNA methyltransferase and hMLH1 in ulcerative colitis-associated tumors: comparison with sporadic colonic tumors

To cast light on the contribution of methylation to genesis of ulcerative colitis (UC)-associated tumors, promoter methylation and expression of O6-methylguanine DNA methyltransferase (MGMT), hMLH1, p16INK4, and E-cadherin were examined in 14 low-grade dysplasias (LGDs), 15 high-grade dysplasias (HG...

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Published in:American journal of clinical pathology 2007-03, Vol.127 (3), p.366-373
Main Authors: Mikami, Tetuo, Yoshida, Tsutomu, Numata, Yoshiko, Shiraishi, Hiroaki, Araki, Kayo, Guiot, Marie-Christine, Jass, Jeremy R, Okayasu, Isao
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Cadherins - genetics
Cadherins - metabolism
Carrier Proteins - genetics
Carrier Proteins - metabolism
Colitis, Ulcerative - genetics
Colitis, Ulcerative - metabolism
Colitis, Ulcerative - pathology
Colonic Neoplasms - genetics
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
DNA Methylation
Gene Frequency
Humans
Immunohistochemistry
MutL Protein Homolog 1
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
O-Methylguanine-DNA Methyltransferase - genetics
O-Methylguanine-DNA Methyltransferase - metabolism
Polymerase Chain Reaction
Promoter Regions, Genetic
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Summary:To cast light on the contribution of methylation to genesis of ulcerative colitis (UC)-associated tumors, promoter methylation and expression of O6-methylguanine DNA methyltransferase (MGMT), hMLH1, p16INK4, and E-cadherin were examined in 14 low-grade dysplasias (LGDs), 15 high-grade dysplasias (HGDs), and 14 adenocarcinomas associated with UC and, for comparison, in 30 sporadic adenomas with LGD, 30 adenomas with HGD, and 60 adenocarcinomas, using methylation-specific polymerase chain reaction and immunohistochemical analysis. The frequency of MGMT and hMLH1 methylation in UC-associated tumors was low, with a significant difference between HGD and sporadic adenomas with HGD of the left hemicolon. The methylation frequency of p16INK4 in UC-associated tumors was also relatively low compared with sporadic colonic tumors. For E-cadherin, methylation was limited in both types of tumor. Decrease of expression of MGMT, hMLH1, and p16INK4 was significantly correlated with methylation. Thus, compared with the sporadic type, contribution of methylation to UC-associated tumorigenesis seems to be low.
ISSN:0002-9173