Hypermethylation of CpG island is a common mechanism by which tumor suppressor genes are inactivated. The tumor suppressor genes p16INK4a and p15INK4b are important components of the cell cycles. We have studied the feasibility of detecting tumor-associated aberrant p16INK4a and p15INK4b methylation in non-small cell lung cancer (NSCLC) using methylation-specific PCR. We found a high frequency of hypermethylation of the p16INK4a gene in 17 of 45 cases of NSCLC. In this study, there was no difference between the clinicopathological features or overall survival of patients with and without p16INK4a methylation. On the other hand, p15INK4b promoter hypermethylation is rare (5/45) in lung cancer and occurs in association with p16INK4a methylation. The overall survival of patients with p15INK4b methylation was markedly shortened in this series. We also analyzed cells in bronchial washings, and p16INK4a methylation was detected in 4 of 17 cases of NSCLC. Moreover, 1 of 10 plasma samples from patients with NSCLC was positive for p16INK4a methylation. Our results suggest a possible prognostic role of p15INK4b methylation in NSCLC, and that the detection of aberrant p16INK4a methylation in both bronchial washings and plasma may be useful for cancer diagnosis.

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