Altered cardia epithelial cell kinetics induced by Helicobacter pylori infection and gastro-oesophageal reflux disease: possible malignant potential?

摘要

BACKGROUND The incidence of adenocarcinoma of the proximal stomach (cardia) is increasing. The pathophysiological processes underlying this trend are unclear. Normal cell turnover depends on cell proliferation being in balance with programmed cell death or apoptosis. It has been well documented that excessive proliferation potentiates the effects of any carcinogen that targets DNA. It is therefore accepted that excessive proliferation is a risk factor for subsequent neoplasia development.AIMS To compare apoptosis and proliferation in normal cardia tissue, carditis, and cardia intestinal metaplasia, and to determine the effect of Helicobacter pylori infection and gastro-oesophageal reflux disease.METHODS Biopsies from the cardia were obtained from consecutive dyspeptic patients and asymptomatic controls at the time of gastroscopy. Samples were assessed histologically and classified as normal, carditis, or cardia tissue with intestinal metaplasia. All samples were then examined, employing immunohistochemical techniques, for the presence of proliferating and apoptotic cells.RESULTS A total of 76 histological specimens were examined. There was a statistical significant difference in the proliferation index between controls and both carditis and cardia intestinal metaplasia, and also between carditis and cardia intestinal metaplasia. In contrast, there was a significant increase in the apoptotic index for carditis compared with controls, while that of intestinal metaplasia did not differ from controls. As a result, comparison of the apoptotic/proliferation ratios for each group revealed that, for both carditis and cardia intestinal metaplasia, the apoptotic index/proliferation index ratio is reduced significantly compared with controls, but as a result of different mechanisms.CONCLUSION This study demonstrates that individuals with carditis and cardia intestinal metaplasia have alterations in epithelial cell kinetics. In particular, it shows that there is a persistent imbalance between proliferation and apoptosis, which may represent malignant potential.