Compartment theory in Helicobacter pylori-associated gastric carcinogenesis

Background: The compartment theory has not been well investigated in gastric carcinogenesis. This study was aimed at examining the compartment alterations through the Helicobacter pylori (H. pylori)-related chronic gastritis-intestinal metaplasia-carcinoma sequence, and investigating the long-term effect of bacterial eradication on the compartment changes. Patients and Methods: Gastric biopsy specimens were obtained from subjects with H. pylori-negative normal mucosa (N = 12), H. pylori-positive non-metaplastic gastritis (N = 42), H pylori-positive intestinal metaplasia (N = 21) and intestinal-type adenocarcinoma (N = 20). The specimens were immnostained for monocloncal antibodies against the proliferating cell nuclear antigen (PCNA) for proliferating analysis. Additionally, 50 patients with H. pylori-positive gastritis were enrolled to investigate the long-term effect of bacterial eradication on the compartment changes of gastric epithelium. Results: The mean PCNA labeling indices (L.I.) of non-metaplastic gastritis, intestinal metaplasia and adenocarcinoma were significantly higher than that of normal mucosa (31.1, 49.2 and 40.7 vs. 21.4; p<0.01, 0.001 and 0.001, respectively). The proliferating zone was principally located in the lower compartment of normal mucosa. In patients with intestinal metaplasia, there was a full expansion (phase 1 change) of proliferating zone to the middle compartment of gastric pits (ratio of L.I. between middle and lower compartment = 1.00). The proliferating cells were evenly distributed in adenocarcinoma (complete loss of compartmentalization). Eradiation of H. pylori led to a reversion of compartment changes of gastric epithelium in patients with chronic gastritis. Conclusion: H. pylori-related gastric carcinognesis is a multistep process involving progressive alterations of proliferating activity as well as loss of compartmentalization. Eradication of H. pylori reverses the changes in growth kinetics of gastric epithelium.