Importance of changes in epithelial cell turnover during Helicobacter pylori infection in gastric carcinogenesis

Abstract

The role of Helicobacter pylori in gastric carcinogenesis is supported almost exclusively by epidemiological data and prospective histopathological studies. From biological and molecular points of view, there is no evidence that H pylori or its cytotoxic products have any mutagenic effects. Nevertheless, this infection is associated with profound changes in the pattern of epithelial cell turnover in gastric glands, though the importance of these changes in gastric carcinogenesis is still controversial. H pylori infection increases cell proliferation and alters the distribution of cycling cells within these glands, but these changes can be reversed by successful eradication of the infection. Apoptosis seems to be increased in gastric epithelial cells during H pylori infection, as shown by in vitro studies. There is some, though no conclusive, evidence that this finding also occurs in H pylori positive subjects. It seems that cagA status influences the effect of H pylori on epithelial apoptosis in infected patients. An association of in vitro H pylori induced apoptosis with changes in the expression of pro- and anti-apoptotic genes is reported in the literature, but further study is necessary to clarify the effect of H pylori infection on the molecular events of the apoptotic pathway.

Figure 1

Bi-directional migration of gastric epithelial cells during the proliferation/differentiation process.

Figure 2

Relation between antral epithelial cell proliferation and mucosal inflammatory cell infiltrate. Computer aided image analysis was used to evaluate acute (polymorphonuclear cells) and chronic (mononuclear cells) inflammation in gastric antral lamina propria from biopsy specimens. Thirty seven subjects, 20 H pylori positive and 17 H pylori negative, were included in the analysis. Consecutive sections (stained with haematoxylin and eosin) from those examined for cell proliferation were evaluated in each case. Mononuclear cells were automatically evaluated using microdensitometric software (Microscience Phoenix Inc.), whereas polymorphonuclear cells were evaluated using software for linear morphometry (Microscience Phoenix Inc.). The number of inflammatory cells counted was expressed as density (cells/mm²). A significant relation was found between total labelling index and both polymorphonuclear and mononuclear cell densities. (Spearman rank test R=0.42; p<0.05).

Figure 3

Apoptotic indexes in 20 H pylori positive and 17 H pylori negative dyspeptic patients. Epithelial apoptosis was assessed using the TUNEL method on antral glands from endoscopic biopsy specimens. The apoptotic index was expressed as the percentage of labelled cells to total cells in each case. Median values are shown by horizontal bars. No significant differences were found between the two groups (Mann-Whitney U test; p=0.07).