Hypermethylation of E-cadherin gene is frequent and independent of p16INK4A methylation in non-small cell lung cancer: potential prognostic implication.

E-cadherin gene is often termed a 'metastasis suppressor' gene and inactivation of this gene through promoter methylation occurs in various epithelial cancer. This study assessed the methylation status of p16 INK4a and E-cadherin genes, correlated with clinical characteristics in lung cancer patients. Forty-five patients with non-small cell lung cancer (NSCLC) were evaluated for methylation status of p16 INK4a and E-cadherin genes by using the methylation-specific PCR. E-cadherin expression in tumor samples was examined by immunohistochemistry. Overall duration of survival in different subsets of NSCLC with or without p16 INK4a or E-cad methylation at diagnosis was compared by using the Kaplan-Meier method and log-rank test. We found the hypermethylation of p16 INK4a gene in 38% (17/45) of our subjects. While the E-cadherin gene was hypermethylated in 62% (28/45) related with reduced E-cadherin expression, and methylation status of both p16 INK4a and E-cadherin genes seemed to be independent. Seventy-six percent (34/45) of NSCLC patients had an abnormal methylation pattern in at least one gene. Although there was no difference in overall survival of patients between methylated p16 INK4a and unmethylated p16 INK4a , NSCLS patients with hypermethylation of both genes (concordant pattern) had a significantly good prognosis. In contrast, NSCLC patients with hypermethylated p16 INK4a but un-methylated E-cadherin gene (discordant pattern) had a significantly poor prognosis. E-cadherin and p16 INK4a are commonly methylated in NSCLC and the methylation pattern of p16 INK4a and E-cadherin genes may have prognostic value for the outcome of NSCLC patients.