Hypermethylation, risk factors, clinical characteristics, and survival in 235 patients with laryngeal and Hypopharyngeal cancers

BACKGROUND. It has been established that promoter hypermethylation occurs in several genes during the pathogenesis of head and neck cancer. The authors investigated the role played by the hypermethylation of 4 cancer-related genes in the survival of patients who had laryngeal and hypopharyngeal cancer and in the occurrence of second primary tumors. METHODS. Archival paraffin-embedded tissue (PET) samples were available from patients who were enrolled in a multicentric European case-control study that was performed between 1979 and 1982 and was followed up to 2000. Genomic DNA extracted from 235 PET samples were analyzed for promoter methylation status of the p16, O-6-methylguanine-DNA methyltransferase (MGMT), death-associated protein kinase (DAP-K), and E-cadherin genes by using a methylation-specific polymerase chain reaction assay. RESULTS. Hypermethylation was present in 44% of samples for p16, in 27% of samples for MGMT in 42% of samples for DAP-K, and in 43% of samples for E-cadherin. Hypermethylation of either individual genes or their combination was not associated with mortality from all causes, mortality from upper aerodigestive tract cancer, or the occurrence of second primary tumors. CONCLUSIONS. The analysis of a large series of patients with laryngeal and hypopharyngeal cancer suggested that hypermethylation is a frequent event in laryngeal and hypopharyngeal cancer, but it is not a predictor of mortality or second primary cancer.