Increased gastric epithelial cell apoptosis associated with colonization with cagA plus Helicobacter pylori strains

Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H, pylori and cancer may be attribu table to increased epithelial cell turnover, possibly related to antigastri c antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expr essing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H, pylori on gastric epithelial prol iferation, apoptosis, and the presence of serum antiparietal cell antibodie s in a large prospective study. Proliferation and apoptosis were evaluated "blindly" using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and resu lts were correlated with the presence of serum antiparietal cell antibodies . H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2 fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increa sed in the antrum and body only in patients with cagA-positive H. pylori st rains. Antiparietal cell antibodies were not more prevalent in H. pylori co lonization, and their presence was inversely related to epithelial apoptosi s scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated,vith increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our resul ts do not support the hypothesis that there is a relative deficiency of gas tric epithelial cell apoptosis associated with the carriage of cage-positiv e strains. Host factors may be more important than bacterial products in de termining the long-term outcome of H. pylori colonization.