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

J Cancer Res Clin Oncol. 2011 Apr;137(4):577-83. doi: 10.1007/s00432-010-0921-9. Epub 2010 May 29.

Abstract

Purpose: 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-α), 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-α induced by H. pylori infection which is involved in the tumor initiation and promotion of gastric carcinogenesis.

Methods: 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-α was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of TNF-α was also studied semiquantitatively by immunohistochemistry.

Results: The RT-PCR and western blotting results of TNF-α 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-α in the similar way.

Conclusion: Over expression of TNF-α showed a significant severity-dose-response as risk markers from preneoplastic lesions to gastric cancer.

MeSH terms

  • Blotting, Western
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism*
  • Gastric Mucosa / immunology
  • Gastritis / immunology
  • Helicobacter Infections / complications*
  • Helicobacter Infections / metabolism
  • Helicobacter pylori*
  • Humans
  • Immunohistochemistry
  • Metaplasia
  • Polymerase Chain Reaction
  • Precancerous Conditions / etiology
  • RNA, Messenger / analysis
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • RNA, Messenger
  • Tumor Necrosis Factor-alpha