DNA methylation and expression of p16(INK4A) gene in pulmonary adenocarcinoma and anthracosis in background lung

The p16 (CDKN2/MTS-I/INK4A) tumor-suppressor gene is frequently inactivated by DNA methylation in lung carcinomas, To clarify whether background anthr acosis may play a role in DNA methylation and inactivation of the p16 gene, we examined DNA methylation of the p16-promoter region by methylation-spec ific polymerase chain reaction, and p16 expression immunohistochemically, a nd compared the results with the level of background anthracosis which was measured by an original quantitative method. At autopsy, DNA methylation of the p16 gene was observed in 6/19 tumors (32%) from patients who had died of pulmonary adenocarcinoma, The degree of background anthracosis (the effe ct of extrinsic carcinogenic factors) (mean absorbance value, A = 0.715) of the cases with p16-gene methylation was significantly higher than that wit hout methylation (mean A value = 0.298). p16 expression was inactivated in all tumors with p16-gene methylation. The mean A value of black dust matter deposition in cases with normal expression of p16 (A = 0.151) was signific antly lower than cases with abnormal expression of p16 (A = 0.531). These r esults indicate that the level of background anthracosis is closely associa ted with inactivation of p16 expression and also DNA methylation of the p16 -gene promoter region in pulmonary adenocarcinogenesis, Int. J. Cancer (Pre d. Oncol.) 84:609-613, 1999. (C) 1999 Wiley-Liss, Inc.