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.