Pathogenesis of Pre-Neoplastic Lesions of the Stomach: Targets for Prevention

Abstract

Gastric atrophy and intestinal metaplasia are generally considered to be precancerous lesions of the stomach. Chronic Helicobacter pylori infection is one the most important factors in the development of these pre-malignant gastric lesions. In addition to bacterial factors, polymorphisms in the cytokine genes of the host that modulate inflammatory responses are found to have a synergistic effect in the development of gastric cancer as well as pre-neoplastic lesions. Recently, inappropriate activation of the intestine-specific transcription factor like the homeobox gene complex CDX1 and CDX2 are found to be an important contributing factor in the induction of intestinal metaplasia in the stomach. Aberrant expression of cyclooxygenase-2 and epigenetic changes are also frequently detected in pre-neoplastic gastric lesions. One of the most important questions relating to these pre-neoplastic gastric lesions is that whether H. pylori eradication could reverse these changes. However, most controlled studies showed no or just modest improvement in intestinal metaplasia after H. pylori eradication. Further studies should evaluate the role of other chemopreventive agents, particularly cyclooxygenase-2 inhibitor, on regression of pre-neoplastic lesions.

Reversibility of atrophic gastritis and intestinal metaplasia after Helicobacter pylori eradication ‐ a prospective study for up to 10 years

“…Thus, although the effect of H. pylori virulent factors will disappear after H. pylori eradication, environmental or host factors might not change so quickly for IM recovery . It has been reported that the appearance of gastric IM is associated with aberrant expression of CDX1 and CDX2, suggesting that the improvement of IM might require down‐regulation of CDX1 and CDX2 . Both CDX1 and CDX2 mRNA levels are decreased with improvement of IM but increased with the aggravation of IM …”

Extensive intestinal metaplasia in gastric carcinoma and in other lesions requiring surgery. A study of 3421 gastrectomy specimens from dwellers of the Atlantic and Pacific basins

“…Because of the continued concern about the importance of IM in gastric carcinogenesis, [24][25][26][27] we thought that it would be interesting to compare the results of the extent of IM obtained in the two basins. We thought that a comparison between the results in the two disparate geographical regions might enable the possible influence of environmental factors upon the development of extensive IM (EIM) in the gastric mucosa to be explored.…”