Proliferative activity of gastric epithelium in progressive stages ofHelicobacter pylori infection

Abstract

Helicobacter pylori (HP) infection is the main etiopathogenetic agent responsible for inflammatory and ulcerative changes in gastroduodenal mucosa and the basis for both intestinal and diffuse types of gastric carcinoma. In this latter case, intestinal metaplasia is the intermediary between gastritis and cancer. In this study we describe the proliferative activity of gastric epithelium in the progressive stages of HP infection. The expression of proliferating cell nuclear antigen (PCNA), which has proven to be a reliable method for this evaluation, was used as a marker. The study was performed on endoscopic biopsies of the gastric antrum of 40 patients, who were divided into five groups, eight in each group: normal histology and endoscopy, HP-; histological HP+ gastritis with normal endoscopy; histological HP+ gastritis with endoscopic evidence of chronic erosions; complete and incomplete intestinal metaplasia in a HP+ stomach. PCNA was detected by immunohistochemistry and expressed as labeling index, ie, percentage of positive nuclei either in the whole or upper third of foveolae. Our data show a progressive increase of epithelial proliferation in the successive stages of HP infection ranging from gastritis alone to the development of incomplete intestinal metaplasia, a well-known precancerous condition. The proliferative pattern tended to expand towards the upper foveolar third, which in normal conditions does not represent a site of epithelial renewal. These alterations may be related to the development of neoplastic transformations of gastric epithelium. It is well known that genetic mutations are facilitated in proliferating cells. Therefore, our results indicate that the high epithelial turnover, expressed by PCNA LI, may be an indicator of increased risk of neoplastic changes in long-standing untreated HP+ chronic gastritis.

Chronic Gastritis

“…The results of these studies may be, in a certain way, compared with own studies according to which no significant influence of H.pylori colonization on proliferative activity of gastric mucosal glandular epithelium was demonstrated. An increase in proliferative activity of glandular epithelium in gastric mucosa was also observed in chronic gastritis, independently of its etiology (Bechi et al, 1996;Deschner et al, 1972;Irazusta et al, 1998;Panella et al, 1996). It was usually accompanied by a decrease in G cell count, including adrenomodulincontaining cells (Kitani et al, 1999), particularly frequently when the gastritis was associated with atrophic lesions.…”

“…It is worth mentioning that other authors (Ito et al, 1986) found a deepening of proliferative zone within gastric glands in the same gastric mucosal inflammatory conditions, with accompanying significant reduction of EC cell number. According to some authors, increased proliferative activity of gastric mucosal glandular epithelium, particularly that measured by PCNA expression, in the course of chronic inflammatory conditions and H.pylori colonization may be even the marker of risk of malignancy development (Irazusta et al, 1998;Panella et al, 1996). Other authors (Diebold et al, 1998), however, demonstrated that during H.pylori colonization a decrease in the number of argyrophilic cells occurs along with simultaneous reduction of their proliferative potential.…”

“…In own studies it has been demonstrated that these regions are the place where the most intensive PCNA expression is observed. Most authors think that proliferative activity of glandular epithelial cells in gastric mucosa increases with Helicobacter pylori colonization (Bechi et al, 1996;Jang & Kim, 2000;Lynch & Axon, 1995;Panella et al, 1996), which is particularly visible in the corpus (Bechi et al, 1996). On the other hand, after eradication, the proliferative activity returns to normal (Lynch & Axon, 1995).…”

Helicobacter pylori infection and expression of DNA mismatch repair proteins

“…Most cells deficient in MMR display a high level of genomic instability characterized by changes in simple repetitive sequences, so-called microsatellite instability (MSI). Chronic H pylori infection damages gastric barrier function [12,13] and stimulates gastric cell proliferation [14][15][16][17][18][19] , which leads to mucosal repair [20] , but which can also induce cellular DNA damage.…”

“…Most cells deficient in MMR display a high level of genomic instability characterized by changes in simple repetitive sequences, so-called microsatellite instability (MSI). Chronic H pylori infection damages the gastric barrier function [12,13] and stimulates gastric cell proliferation [14][15][16][17][18][19] , which leads to mucosal repair [20] , but which can also induce cellular DNA damage [18][19][20][21][22] . H pylori gastritis occurs more frequently in individuals with MSI-positive than MSI-negative gastric cancers, which raises the possibility that H pylori infection affects the DNA MMR system [23] .…”