Effect of eradication of Helicobacter pylori on genetic instabilities in gastric intestinal metaplasia

Abstract

Summary Background There is little evidence of changes in genetic variations in gastric intestinal metaplasia (GIM) after the eradication of Helicobacter pylori (H. pylori). Aim To investigate the effects of H. pylori eradication on genetic GIM variability in patients with and without gastric cancer in a one‐year prospective study. Methods We analysed microsatellite instability (MSI) and loss of heterozygosity (LOH) in GIM. Subjects included Gr. A (n = 39): chronic gastritis, and Gr. B (n = 53): intestinal‐type early gastric cancer patients who underwent endoscopic mucosal resection (n = 25) and surgical resection (n = 28). Results The frequency of incidence of MSI in GIM was 10.3% and 28.3% for Gr. A and Gr. B, respectively. Gr. B showed a significantly (p = 0.03) higher incidence rate than Gr. A for MSI, but not for LOH. The frequency of MSI declined in both groups post‐eradication, and patients that were positive for MSI before treatment were negative after H. pylori eradication. Unfortunately, however, GIM scores did not decline significantly post‐treatment for either group. Conclusions MSI in GIM may be associated with gastric carcinogenesis. H. pylori eradication reduced MSI during the one‐year post‐treatment period, although no histological improvement in GIM was observed. These changes in MSI may explain the decrease in gastric cancer incidence after the eradication of H. pylori.

Effect of Eradication of Helicobacter pylori on the Histology and Cellular Phenotype of Gastric Intestinal Metaplasia

“…Indeed, we recently found that cell kinetics and genetic alterations (ie, microsatellite instability and K-ras mutations in GIM), play a role in the early events leading to gastric carcinogenesis, and H pylori eradication settled these genetic events only during the 1-year posttreatment period. 32,65 Taking our present and previous data 32, 65 together, eradication of H pylori may inhibit this intracellular dysfunction, which thereby may inhibit carcinogenesis.…”

“…7,8 The 96 H pylori-positive patients were divided into 3 groups on the basis of history and initial histology by a single experienced pathologist. Group CG (n ϭ 36) had histologically 23 Duodenal ulcer (n ϭ 32) 85 mo van der Hulst et al 24 Dyspepsia and peptic ulcer (n ϭ 106) 1 y Hibi et al 25 Gastric ulcer (n ϭ 16) 6 mo Duodenal ulcer (n ϭ 9) Satoh et al 26 Atrophic gastritis (n ϭ 20) 12-33 mo Tucci et al 27 Fundic atrophic gastritis (n ϭ 20) 3 y Tepes et al 28 Duodenal ulcer (n ϭ 63) 4 y El-Omar et al 29 Cancer patients' relatives (n ϭ 40) 1 y Kim et al 30 Gastric ulcer (n ϭ 41) 2 y Duodenal ulcer (n ϭ 72) Kuipers et al 31 Reflux esophagitis (n ϭ 231) 2 y Tanaka et al 32 Atrophic gastritis (n ϭ 39) 1 y chronic gastritis, but no GIM. This group was considered to correspond to nonmetaplastic multifocal atrophic gastritis according to the global diagnosis by Mera et al 20 Thirty of the 36 patients had peptic ulcers, comprising 34 gastric ulcers and 2 gastroduodenal ulcers, and 6 patients had chronic gastritis without ulcer.…”

“…Some studies reported that the histologic grade of GIM had improved after eradication, [12][13][14][15][16][17][18][19][20][21] but other studies did not find any change. [22][23][24][25][26][27][28][29][30][31][32] Some of the reasons for these discrepancies may be ethnic variations, completeness of eradication, stage of the disease when treatment was initiated, and the short follow-up period (in most studies the follow-up period did not exceed 1 year). 17,23,27,28,30,32 We developed a monoclonal antibody (mAb), Das-1 (formerly known as 7E 12 H 12 , immunoglobulin [Ig]M isotype), that specifically reacts with colonic epithelium 33 (both goblet and nongoblet absorptive cells), but not with enterocytes (including goblet cells) from jejunum or ileum and normal epithelium from the stomach and esophagus.…”

“…[22][23][24][25][26][27][28][29][30][31][32] Some of the reasons for these discrepancies may be ethnic variations, completeness of eradication, stage of the disease when treatment was initiated, and the short follow-up period (in most studies the follow-up period did not exceed 1 year). 17,23,27,28,30,32 We developed a monoclonal antibody (mAb), Das-1 (formerly known as 7E 12 H 12 , immunoglobulin [Ig]M isotype), that specifically reacts with colonic epithelium 33 (both goblet and nongoblet absorptive cells), but not with enterocytes (including goblet cells) from jejunum or ileum and normal epithelium from the stomach and esophagus. 33,34 However, mAb Das-1 reacts sensitively (95%) and specifically (100%) to Barrett's epithelium, a preneoplastic condition of the esophagus, and adenocarcinoma of the esophagus.…”

Mucosal barrier defects in gastric intestinal metaplasia: in vivo evaluation by confocal endomicroscopy

“…[6][7][8][9][10][11] The discrepancies are partly due to the patchy distribution of IM, making IM difficult to assess by using limited random biopsy specimens and leading to imprecise results as a consequence of sampling errors.…”