title: Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia.
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.
authors: Department of Physiology, University of Porto, Porto, Portugal. pedronunesml@gmail.com
authors: Pedro
authors: P
authors: Pimentel-Nunes
authors: Luís
authors: L
authors: Afonso
authors: Paula
authors: P
authors: Lopes
authors: Roberto
authors: R
authors: Roncon-Albuquerque
authors: Nádia
authors: N
authors: Gonçalves
authors: Rui
authors: R
authors: Henrique
authors: Luís
authors: L
authors: Moreira-Dias
authors: Adelino F
authors: AF
authors: Leite-Moreira
authors: Mário
authors: M
authors: Dinis-Ribeiro
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008679:Metaplasia / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5