Helicobacter pylori associated chronic gastritis, clinical syndromes, precancerous lesions, and pathogenesis of gastric cancer development

Abstract

Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the "point of no return" and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.

Keywords: Eradication; Gastric atrophy; Gastric cancer; Helicobacter pylori; Intestinal metaplasia; Molecular alteration; Prevention.

Figure 1

Serial sections of formalin fixed paraffin embedded biopsy tissue from two patients with gastric intestinal metaplasia without carcinoma. Haematoxylin-eosin staining (A, D), alcian blue/high iron diamine staining (B, E), and immunoperoxidase assay with the monoclonal antibody mAb Das-1 (C, F); (A-C) is from the same patient and (D-F) from the second patient. mAb Das-1 stained both goblet cells (shorter arrow) and metaplastic non-goblet cells (longer arrow) in the glands (C), suggesting colonic phenotype (incomplete type); While GIM is clearly evident with the presence of goblet cells (D, E) in the second patient, but mAb Das-1 did not stain the glands including goblet cells (F). The arrow shows the unstained goblet cells suggesting complete phenotype or small intestinal phenotype (original magnification × 160 for each part)[106].