Premium
CDKN2A promoter methylation is related to the tumor location and histological subtype and associated with Helicobacter pylori fla A(+) strains in gastric adenocarcinomas
Author(s) -
ALVES MARKÊNIA KÉLIA SANTOS,
LIMA VALESKA PORTELA,
FERRASI ADRIANA CAMARGO,
RODRIGUES MARIA APARECIDA,
DE MOURA CAMPOS PARDINI MARIA INÊS,
RABENHORST SILVIA HELENA BAREM
Publication year - 2010
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2010.02591.x
Subject(s) - helicobacter pylori , methylation , cdkn2a , dna methylation , adenocarcinoma , biology , cancer research , medicine , cancer , gastroenterology , gene , genetics , gene expression
Alves MKS, Lima VP, Ferrasi AC, Rodrigues MA, de Moura Campos Pardini MI, Rabenhorst SHB. CDKN2A promoter methylation is related to the tumor location and histological subtype and associated with Helicobacter pylori fla A(+) strains in gastric adenocarcinomas. APMIS 2010; 118: 297–307. Promoter hypermethylation of CDKN2A (p16 INK4A protein) is the main mechanism of gene inactivation. However, its association with Helicobacter pylori infection is a controversial issue. Therefore, we examined a series of gastric adenocarcinomas to assess the association between p16 INK4A inactivation and H. pylori genotype ( va cA, cag A, cag E, vir B11 and fla A) according to the location and histological subtype of the tumors. p16 INK4A expression and CDKN2A promoter methylation were found in 77 gastric adenocarcinoma samples by immunohistochemistry and methylation‐specific PCR, respectively. Helicobacter pylori infection and genotype were determined by PCR. A strong negative correlation between immunostaining and CDKN2A promoter region methylation was found. In diffuse subtype tumors, the inactivation of p16 INK4A by promoter methylation was unique in noncardia tumors (p = 0.022). In addition, H. pylori ‐bearing fla A was associated with non‐methylation tumors (p = 0.008) and H. pylori strain bearing cag A or vac As1m1 genes but without fla A was associated with methylated tumors (p = 0.022 and 0.003, respectively). Inactivation of p16 INK4A in intestinal and diffuse subtypes showed distinct carcinogenic pathways, depending on the tumor location. Moreover, the process of methylation of the CDKN2A promoter seems to depend on the H. pylori genotype. The present data suggest that there is a differential influence and relevance of H. pylori genotype in gastric cancer development.