Promoter Methylation of E-cadherin Gene in Gastric Mucosa Associated with Helicobacter Pylori Infection and in Gastric Cancer

Overview

Journal Gut

Specialty Gastroenterology

Date 2003 Mar 13

PMID 12631658

Citations 118

Authors

A O-O Chan

S-K Lam

B C-Y Wong

W-M Wong

M-F Yuen

Y-H Yeung

W-M Hui

A Rashid

Y-L Kwong

Affiliations

Soon will be listed here.

Abstract

Background: E-cadherin is an adhesion molecule involved in tumour invasion/metastasis. Silencing of E-cadherin by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. Helicobacter pylori is a class I carcinogen in gastric cancer.

Aims: This study was undertaken to investigate the association between methylation of E-cadherin and H pylori in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer.

Methods: E-cadherin methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. E-cadherin expression was studied by immunohistochemistry.

Results: E-cadherin methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with H pylori infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. E-cadherin methylation was present in 0% (0/8) of normal mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. E-cadherin methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. E-cadherin methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05).

Conclusion: E-cadherin methylation is an early event in gastric carcinogenesis, and is initiated by H pylori infection.

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