Altered gastric epithelial cell kinetics in Helicobacter pylori-associatedintestinal metaplasia: Implications for gastric carcinogenesis

We have compared apoptosis and proliferation in antral epithelium from indi viduals not infected with H. pylori (Hp), those with Hp-induced gastritis a nd those with Hp-induced gastritis containing areas of gastric intestinal m etaplasia, the precursor lesion to gastric adenocarcinoma. Antral biopsies from 42 patients were assessed for evidence of Hp infection, severity of ga stritis and intestinal metaplasia. Apoptosis was evaluated by the TUNEL ass ay and proliferation by Ki-67 immunohistochemistry and were expressed as ap optotic (Al) and proliferation (PI) indices. In the 31 Hp-positive (Hp(+)) patients, apoptosis and proliferation were increased compared with the 11 H p-negative (Hp(-)) patients (AI = 1.22 +/- 0.13% vs. 0.15 +/- 0.03%, p < 0. 0001; PI = 24 +/- 1% vs. 13 +/- 2%, p < 0.0001), Increases were proportiona l to the severity of the inflammation. Within foci of intestinal metaplasia , in 9 of the Hp(+) patients, apoptosis was significantly reduced compared with surrounding gastritis(Al = 0.20 +/- 0.06% vs. 1.34 +/- 0.23%, p = 0.00 14), whereas proliferation was not altered (PI = 25.4 +/- 4% vs. 24.7 +/- 2 %, p = 0.87), resulting in a lower AI/PI ratio in intestinal metaplasia tha n in surrounding gastritis (0.008 +/- 0.005 vs. 0.054 +/- 0.009, p < 0.02). Hp-induced gastritis is thus associated with increased epithelial apoptosi s and proliferation compared with uninfected controls. In intestinal metapl asia, proliferation remains increased but apoptosis reverts to normal level s, and this perhaps contributes to Hp-associated gastric carcinogenesis. In t, J. Cancer 85:192-200,2000. (C) 2000 Wiley-Liss, Inc.