Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia

Pathol Oncol Res. 2011 Sep;17(3):677-83. doi: 10.1007/s12253-011-9368-9. Epub 2011 Apr 1.

Abstract

TLRs are important innate immunity receptors. Even though TLR2, 4 and 5 appear to be important for Helicobacter pylori (HP) recognition, their role in the evolution of gastritis to more advanced lesions is still unknown. To compare the expression of TLR2, 4 and 5 in normal gastric mucosa, HP+ gastritis, intestinal metaplasia, dysplasia and adenocarcinoma. Immunohistochemistry for TLR2, 4 and 5 was performed with anti-TLR2-TLR4-TLR5 antibodies in 117 histological samples of normal gastric mucosa (n = 22), HP+ gastritis (n = 20), intestinal metaplasia (n = 33), dysplasia (mucosectomy specimens, n = 20) and intestinal type adenocarcinoma (surgery specimens,n = 22); quantification of expression was performed independently by two pathologists taking into account the percentage of positive epithelial cells and the degree of expression (zero to three score). A statistically significant trend for progressive increase of TLRs expression from normal mucosa to gastric dysplasia was found (mean expression: normal mucosa 0.1; gastritis 1.0; metaplasia 2.2; dysplasia 2.8, p < 0.01). All dysplasia samples presented more than 90% positive epithelial cells with strong expression (2.8;95%CI2.7-3). There was less TLRs expression in carcinomas (TLR2:1.0; TLR4:2.0 and TLR5:1.2, p < 0.05) when compared with dysplasia, with TLR4 being more expressed than TLR2 and 5 in these lesions (p = 0.03). A score of all markers' expression of eight leads to a low (4%) false positive rate in patients with precancerous conditions. Progression of gastric lesions associated with gastric carcinogenesis is associated with increased TLRs expression. Gastric dysplasia presents a high level of TLRs expression, suggesting that these receptors may play a role in adenocarcinoma development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Case-Control Studies
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastritis / metabolism
  • Gastritis / pathology
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology
  • Metaplasia / metabolism*
  • Metaplasia / pathology
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Prognosis
  • Sensitivity and Specificity
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / metabolism*
  • Toll-Like Receptor 5 / metabolism*

Substances

  • TLR2 protein, human
  • TLR4 protein, human
  • TLR5 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 5