Molecular and histological evaluation of tumor necrosis factor-alpha expression in Helicobacter pylori-mediated gastric carcinogenesis

Helicobacter pylori (H. pylori) is considered to be a major factor contributing to gastric mucosal damage by stimulating mucosal macrophage production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), but the inflammatory responses within the gastric mucosa in vivo are not well known. Therefore, this study was designed to investigate the expression of TNF-alpha induced by H. pylori infection which is involved in the tumor initiation and promotion of gastric carcinogenesis. This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status has been analyzed. The expression of TNF-alpha was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of TNF-alpha was also studied semiquantitatively by immunohistochemistry. The RT-PCR and western blotting results of TNF-alpha mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of TNF-alpha in the similar way. Over expression of TNF-alpha showed a significant severity-dose-response as risk markers from preneoplastic lesions to gastric cancer.