p16(INK4a) Promoter hypermethylation of non-tumorous tissue adjacent to gastric cancer is correlated with glandular atrophy and chronic inflammation

The p16(INK4a) tumor suppressor gene can be inactivated by promoter region hypermethylation in many tumor types including gastric cancers. However, p16(INK4a) promoter hypermethylation in the surrounding non-tumorous tissues of gastric cancers has not been studied in detail. We therefore examined 46...

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Bibliographic Details
Published in:International journal of cancer 2001-09, Vol.93 (5), p.629
Main Authors: Jang, T J, Kim, D I, Shin, Y M, Chang, H K, Yang, C H
Format: Article
Language:English
Subjects:
Atrophy - genetics
Blotting, Western
Chronic Disease
Cyclin-Dependent Kinase Inhibitor p16 - genetics
DNA Methylation
Gene Expression Regulation, Neoplastic
Humans
Inflammation - genetics
Promoter Regions, Genetic - genetics
Stomach - physiology
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
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Summary:The p16(INK4a) tumor suppressor gene can be inactivated by promoter region hypermethylation in many tumor types including gastric cancers. However, p16(INK4a) promoter hypermethylation in the surrounding non-tumorous tissues of gastric cancers has not been studied in detail. We therefore examined 46 gastric cancers, corresponding adjacent non-tumorous tissue samples and 8 gastric tissue samples of chronic gastritis by performing methylation-specific polymerase chain reaction, and we analyzed p16(INK4a) protein expression using immunohistochemistry and Western blot. p16(INK4a) promoter hypermethylation was observed in 43% of gastric cancers and 59% of adjacent non-tumorous tissues; however, none of the samples retrieved from the chronic gastritis patients displayed p16(INK4a) promoter hypermethylation. Gastric cancers showed an inverse correlation between vascular invasion and p16(INK4a) promoter hypermethylation, and adjacent non-tumorous tissues displayed a close association among the grade of chronic inflammation, presence of glandular atrophy and p16(INK4a) promoter hypermethylation. p16(INK4a) expression was markedly decreased in samples with p16(INK4a) promoter hypermethylation when compared with samples without p16(INK4a) promoter hypermethylation. These results suggest that p16(INK4a) promoter hypermethylation is an early and frequent event in gastric carcinogenesis and may serve as a new prognostic biomarker for the risk of gastric cancers.
ISSN:0020-7136
DOI:10.1002/ijc.1394