Effects of Helicobacter pylori infection on genetic instability, the aberrant CpG island methylation status and the cellular phenotype in Barrett's esophagus in a Japanese population

Abstract

Genetic or epigenetic alterations in Barrett's esophagus (BE) with/without Helicobacter pylori (H. pylori) infection remain unclear. We examined the effects of H. pylori infection on genetic instability (GIN), the CpG island methylation status and a biomarker related to BE carcinogenesis. We analyzed 113 Japanese individuals with endoscopically suspected BE. The patients included, Group CLE (n 5 25): no specialized intestinal metaplasia (SIM) in a columnar lined epithelium (control); Group BE (n 5 88): all had SIM. Microsatellite instability and a loss of heterozygosity as GIN, the methylation status at hMLH1, E-cadherin, p16 and APC, and immunoreactivity using a monoclonal antibody (mAb) Das-1, which specifically reacts with BE, were evaluated. Nine additional patients with BE were prospectively followed up for 2 years after successful H. pylori eradication. The frequency of GIN, methylation at E-cadherin and APC, and mAb Das-1 reactivity in Group BE was significantly higher than that in Group CLE (p < 0.0001, p < 0.0001 and p < 0.005, and p < 0.0001, respectively). Furthermore, GIN, E-cadherin methylation and mAb Das-1 reactivity showed a significantly higher incidence in patients with H. pylori infection than in those without H. pylori infection (p < 0.01, p < 0.005, and p < 0.01, respectively). Interestingly, the patients from Group BE were observed to change to a stable state of molecular alterations in 60% for GIN, 42.9% for E-cadherin methylation and 55.6% for APC methylation, or a reduction of mAb Das-1 reactivity was noted in 25% following eradication. H. pylori infection may therefore affect these molecular alterations associated with the pathogenesis of BE, to some degree, in the Japanese population. '

Localization of specialized intestinal metaplasia and the molecular alterations in Barrett esophagus in a Japanese population: an analysis of biopsy samples based on the “Seattle” biopsy protocol

“…With regard to MSI, there have been several reports with similar findings, including our previous study, in which there was a positive association between MSI and BE or EAC, and in which MSI in BE was found to take place earlier in the development of SIM [29,32]. Thus, the genetic, as well as epigenetic, alterations present in EAC may already be present in BE [29,32].…”

“…Thus, the genetic, as well as epigenetic, alterations present in EAC may already be present in BE [29,32]. Although the incidence of molecular changes in SIM and CLE was slightly different from that found in our previous study [29], this might be accounted for by differences in the sample size and method of molecular analysis.…”

“…DNA was extracted only from cancer cells, SIM, or CLE glands in the biopsy samples via laser capture microdissection (LCM) using the PALM MicroBeam (Microlaser Technologies, Munich, Germany) to avoid DNA contamination of inflammatory or stromal cell nuclei based on the methodology previously described [28,29] (Supplementary Fig. S1).…”

“…As reported [29], we examined five microsatellite loci on chromosomes for MSI based on the revised Bethesda panel [30] as follows: BAT26, BAT25, D2S123, D5S346, and D17S250. The PCR products were evaluated for MSI by capillary electrophoresis using an ABI PRISM ® 310 Genetic Analyzer (Applied Biosystems, Foster City, CA) and automatic sizing of the alleles using a GeneMapper ® (Applied Biosystems).…”

Gallstones increase the prevalence of Barrett’s esophagus

“…The association of the presence of H. pylori infection or the severity of gastric mucosal atrophy with the presence of ESEM was still controversial [41,44,45]. In general, many studies have shown that H. pylori infection and gastric mucosal atrophy are inversely associated with BE [25,46].…”