H pylori (CagA) and Epstein-Barr virus infection in gastric carcinomas: Correlation with p53 mutation and c-Myc, Bcl-2 and Bax expression

Abstract

AIM: To investigate the interrelationship betweenH pylori and Epstein-Barr virus (EBV) infection in the gastric carcinogenesis having in focus the p53 mutation and the c-Myc, Bcl-2 and Bax expression.METHODS: seventy-one gastric carcinoma tissues were assessed by polymerase chain reaction (PCR) for H pylori and in situ hybridization for EBV. c-Myc, Bcl-2 and Bax expression were detected by immunohistochemistry and single-stranded conformational polymorphism (SSCP) for p53 mutation. RESULTS:The positivity rates for H pylori and EBV were 94.4% and 8.45%, respectively. The majority of the cases displayed only the H pylori presence. All EBV positive cases were also H pylori positive. None infectious agent was observed in 5.55% of the cases. The intestinal type tumor was more frequent in the co-infected and non-infected groups. The female predominated in the non-infected group showing statistical significance (70.4% vs 29.6%, P = 0.039). The Bcl-2 was only detected in the group exclusively infected by H pylori .However, c-Myc and Bax were detected in the three groups but with a low frequency in the co-infected group. Mutation of p53 was present in all groups, with the highest frequencies in the H pylori positive groups. CONCLUSION:The frequency of H pylori infection in gastric carcinomas was high. The presented data indicated that gastric carcinogenesis has different pathways depending of the presence of the two investigated infectious agents, suggesting a possible involvement of H pylori with apoptotic process. The low expression of c-Myc and Bax in the EBV-positive groups suggests that EBV may inhibit the expression of these proteins. Nevertheless, p53 mutation shows to be a relevant alteration, independent of both infectious agents.

MYC and gastric adenocarcinoma carcinogenesis

“…It was inferred that EBV might cause the host cell to induce MYC expression in early cancer development, but then negatively affect MYC expression in advanced stages of cancers, making them less likely to have a natural regression via apoptosis. Lima et al [58] also reported MYC low expression in EBV-positive GC samples. However, Luo et al [67] have not found any correlation between EBV and MYC expression in GC, suggesting that EBV does not inhibit MYC expression in advanced stages of EBVpositive gastric cancer.…”

“…EBV infection is seen in about 10% of gastric adenocarcinoma cases [49,58,67] . Ishii et al [49] found MYC expression in early stages of EBV-positive GC was higher than that of EBV-negative GC, while MYC expression in advanced stages of EBV-positive GC was lower than that of EBV-negative tumors.…”

Epstein-Barr Virus-Associated Gastric Carcinoma: Use of Host Cell Machineries and Somatic Gene Mutations

“…Camargo et al [14] recently reported that smoking is a risk factor for EBVaGC (odds ratio of 1.5; 95% CI 1.01-2.3). The frequency of Helicobacter pylori infection is controversial; some reports indicate less frequent H. pylori infection in EBVaGC [15,16], while others indicate that the infection frequency is higher in EBVaGC than in other gastric cancers [17,18]. However, the background mucosa in EBVaGC is characterized by severe atrophic gastritis with a paucity of intestinal metaplasia [17,19].…”

Factores genéticos y epigenéticos del cáncer gástrico

“…La sobreexpresión de MYC se asocia con tumores más agresivos, principalmente en CG-TI (Panani 2008) y con mal pronóstico (de Souza et al 2013, Nobili et al 2011, Panani y Roussos 2005. Finalmente, la infección por de H. pylori cagA+ aumenta la sobreexpresión de MYC en mucosa gástrica (Lima et al 2008).…”