Expression of Bile Acid Receptor TGR5 in Gastric Biopsies with Intestinal Metaplasia Correlates with p53 Protein Accumulation

Abstract

Introduction: Bile has been shown to be genotoxic and plays a role in gastric intestinal metaplasia and tumorigenesis. The bile acid receptor TGR5 was found to be expressed in the majority of intestinal type gastric adenocarcinoma. p53 protein accumulation as detected by immunohistochemistry (IHC) and p53 gene mutation have been detected in gastric precancerous lesions including intestinal metaplasia. The aim of this study was to determine whether TGR5 is expressed in gastric intestinal metaplasia, a precursor for intestinal-type adenocarcinoma, and to correlate this expression with clinicopathologic parameters and with p53 protein accumulation. Methods: TGR5 and p53 expression in sections of formalin fixed paraffin embedded gastric biopsies from 58 consecutive patients with gastric metaplasia were determined by IHC. TGR5 expression was correlated with p53 protein accumulation, Helicobacter pylori status, patient gender and age, history of cholecystectomy, and body mass index (BMI). Results: Thirty-four (59%) of the 58 biopsies with intestinal metaplasia showed TGR5 expression in the gastric epithelium and 24 (41%) were negative. There was no difference between patients with TGR5-positive and TGR5-negative biopsies in median age (64 years vs 61 years, p=0.658), sex (50% males vs 50% females), median BMI (28.86 vs 25.52, p=0.126), Helicobacter pylori status (positive in 32% vs 29%, p=0.796), or history of cholecystectomy (28% vs 27%, p=0.945). Eleven (42%) of the TGR5-positive biopsies were positive for p53 compared to 2 (8%) of the TGR5-negative biopsies (p=0.03). There was no significant association between Helicobacter pylori status and p53 positivity. Three (17%) of 18 biopsies with history of positive Helicobacter pylori were positive for p53 protein accumulation compared to 10 (25%) of 40 with negative Helicobacter pylori (p=0.48). Conclusion: In our patient population with intestinal metaplasia, 60% of the biopsies show TGR5 expression. Significantly more biopsies with TGR5 expression overexpress the p53 protein. Follow-up studies are needed to determine whether TGR5 expression precedes p53 overexpression in gastric biopsies with intestinal metaplasia and to explore its utility as a biomarker for selecting patients for prevention studies.