Methylation of E-cadherin gene in gastric cancer and in normal gastric mucosa from patients with and wihtout Helicobacter pylori infection

Abstract

INTRODUCTION: E(epithelial)-cadherin is an important homotypic adhesion molecule which plays important role in tumor invasion/metastasis. Silencing of E-cadherin by CpG island methylation has been identified to be an important mechanism in both familial and sporadic gastric cancer. AIM: We investigated methylation of E-cadherin in normal gastric mucosa from normal subjects, and intestinal metaplasia, adenocarcinoma, and metastatic lymph nodes from patients with gastric cancer. METHODS: Methylation at E-cadherin was studied by methylation-specific polymerase chain reaction (MSP) and expression of E-cadherin by immunohistochemical staining. All statistical studies were two-sided. Results CpG island methylation was identified in 30% of normal gastric mucosa. Significant association between methylation and Helicobacter pylori was observed: 90% of methylated mucosa were H. pylori + ve, vs. 65% of unmethylated mucosa were H. pylori—ve (P = 0.002). Methylation in mucosa increases with age (P = 0.04). Methylation was observed in 59% of intestinal metaplasia, 58% of tumorous tissues, and 60% of metastatic lymph nodes. Concordancy rate of methylation status between different stages in the same patient was 83%. Methylation at E-cadherin correlated with lymph node metastasis (P = 0.046), and was observed more frequently in mucinous and signet ring cell tumors (P = 0.0058). CONCLUSION: A possible link exists among E-cadherin methylation, Helicobacter pylori and aging. This may provide clue for the initiating mechanism of methylation.