Diagnostic Role of RASSF1A and p16INK4a Promoter Gene Hypermethylation in Serum DNA of Lung Cancer Patients: Clinicopathological Significance.

The most common inactivation mechanism of tumor suppressor genes, RASSF1A and p16INK4a, in lung cancer is hypermethylation. We detected the methylation status of RASSF1A and p16INK4a in serum of lung cancer patients using methylation-specific PCR and analyzed their clinicopathological significance. Each of RASSF1A and p16INK4a hypermethylation was detected in 31.1% cancer patients but not in benign lung lesion patients. Hypermethylation was preferentially observed in small cell lung cancer (SCLC) for RASSF1A (50%), but not for p16INK4a. In non-small cell lung cancer (NSCLC), RASSF1A and p16INK4a hypermethylation were found in 27% and 37.8% respectively. Hypermethylation of RASSF1A was not correlated with clinicopathological character. While, p16INK4a hypermethylation was associated with age >60 years, smoking and squamous cell carcinoma (SCC) (P = 0.033), but not with gender and pathological stages of NSCLC. Sensitivity and specificity of each gene were 31.1% and 100% respectively and the sensitivity improved with evaluation of a combination of the two genes (55.6%). These findings suggest that serum RASSF1A and p16INK4a hypermethylation are promising diagnostic method for detection of lung cancer. As regard the clinicopathological characteristics, p16INK4a hypermethylation may provide a more specific approach than RASSF1A hypermethylation.