Altered gastric epithelial cell kinetics in Helicobacter pylori-associated intestinal metaplasia: implications for gastric carcinogenesis.
We have compared apoptosis and proliferation in antral epithelium from individuals not infected with H. pylori (Hp), those with Hp-induced gastritis and those with Hp-induced gastritis containing areas of gastric intestinal metaplasia, the precursor lesion to gastric adenocarcinoma. Antral biopsies from 42 patients were assessed for evidence of Hp infection, severity of gastritis and intestinal metaplasia. Apoptosis was evaluated by the TUNEL assay and proliferation by Ki-67 immunohistochemistry and were expressed as apoptotic (AI) and proliferation (PI) indices. In the 31 Hp-positive (Hp(+)) patients, apoptosis and proliferation were increased compared with the 11 Hp-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 proportional 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 (AI = 0.20 +/- 0.06% vs. 1.34 +/- 0.23%, p = 0. 0014), 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 than in surrounding gastritis (0.008 +/- 0.005 vs. 0.054 +/- 0.009, p < 0.02). Hp-induced gastritis is thus associated with increased epithelial apoptosis and proliferation compared with uninfected controls. In intestinal metaplasia, proliferation remains increased but apoptosis reverts to normal levels, and this perhaps contributes to Hp-associated gastric carcinogenesis.
Scotiniotis
I A
IA
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Rokkas
T
T
Furth
E E
EE
Rigas
B
B
Shiff
S J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000150:complications / Q000473:pathology*; D016480:Helicobacter pylori; D006801:Humans; D020287:In Situ Nick-End Labeling; D007422:Intestines / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000209:etiology; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology