Alteration of O6-methylguanine-DNA methyltransferase in colorectal neoplasms in sporadic and familial adenomatous polyposis patients.
DNA repair failure is known to be a critical event during carcinogenesis of colorectal cancers. To investigate whether O(6)-methylguanine-DNA methyltransferase (MGMT) is altered during colorectal carcinogenesis, we performed immunohistochemical staining on 265 sporadic colorectal cancers, 113 sporadic adenomas, 33 familial adenomatous polyposis (FAP) colorectal cancers, and 93 FAP adenomas. Sixty-seven of 265 sporadic colorectal cancer cases and five of 113 sporadic adenoma cases showed loss of MGMT expression (P < 0.001). Among FAP patients, four of 33 cancers and six of 93 adenomas showed loss of MGMT protein expression. When we compared the association between MGMT promoter hypermethylation and protein expression, almost all cases without a methylated allele were positive for the expression of MGMT. In contrast, cases with promoter methylation frequently showed loss of MGMT expression (P < 0.01). Loss of MGMT was correlated with some clinicopathological characteristics, i.e., tumor invasion (P = 0.013) and stage (P = 0.035) in sporadic colorectal cancer, and degree of atypism (P = 0.042) in sporadic adenoma. Our results show that loss of expression of MGMT occurs more frequently in cancer than in adenoma in both sporadic and FAP patients, and that loss of expression of MGMT is associated with hypermethylation of the promoter area of MGMT gene.
Department of Pathology and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Sun Hee
SH
Kim
Soo In
SI
Bae
Hye Seung
HS
Lee
Woo Ho
WH
Kim
D000236:Adenoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D011125:Adenomatous Polyposis Coli / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D019853:O(6)-Methylguanine-DNA Methyltransferase