title: Hypermethylation of E-cadherin gene is frequent and independent of p16INK4A methylation in non-small cell lung cancer: potential prognostic implication.
abstract: 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 p16INK4a 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 p16INK4a 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 p16INK4a or E-cad methylation at diagnosis was compared by using the Kaplan-Meier method and log-rank test. We found the hypermethylation of p16INK4a 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 p16INK4a 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 p16INK4a and unmethylated p16INK4a, NSCLS patients with hypermethylation of both genes (concordant pattern) had a significantly good prognosis. In contrast, NSCLC patients with hypermethylated p16INK4a but un-methylated E-cadherin gene (discordant pattern) had a significantly poor prognosis. E-cadherin and p16INK4a are commonly methylated in NSCLC and the methylation pattern of p16INK4a and E-cadherin genes may have prognostic value for the outcome of NSCLC patients.
authors.affiliation: Social Insurance Kamata General Hospital, Ohta-ku, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
authors.forename: Junko H
authors.initials: JH
authors.lastname: Ohyashiki
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013447:Sulfites / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D013447:Sulfites