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p16 INK4a Promoter hypermethylation of non‐tumorous tissue adjacent to gastric cancer is correlated with glandular atrophy and chronic inflammation
Author(s) -
Jang Tae Jung,
Kim Dae In,
Shin Yeon Myung,
Chang Hee Kyung,
Yang Chang Heon
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1394
Subject(s) - dna methylation , cancer , methylation , immunohistochemistry , carcinogenesis , tumor suppressor gene , biology , cancer research , chronic gastritis , pathology , promoter , atrophic gastritis , medicine , stomach , gene expression , gastritis , gene , biochemistry , genetics
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. © 2001 Wiley‐Liss, Inc.