DNA methylation and expression of p16(INK4A) gene in pulmonary adenocarcinoma and anthracosis in background lung.
The p16 (CDKN2/MTS-1/INK4A) tumor-suppressor gene is frequently inactivated by DNA methylation in lung carcinomas. To clarify whether background anthracosis may play a role in DNA methylation and inactivation of the p16 gene, we examined DNA methylation of the p16-promoter region by methylation-specific polymerase chain reaction, and p16 expression immunohistochemically, and 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 effect of extrinsic carcinogenic factors) (mean absorbance value, A = 0.715) of the cases with p16-gene methylation was significantly higher than that without 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 significantly lower than cases with abnormal expression of p16 (A = 0.531). These results indicate that the level of background anthracosis is closely associated with inactivation of p16 expression and also DNA methylation of the p16-gene promoter region in pulmonary adenocarcinogenesis. Int. J. Cancer (Pred. Oncol.) 84:609-613, 1999.
Hou
M
M
Department of Pathology, Institute of Basic and Clinical Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Morishita
Y
Y
Iljima
T
T
Inadome
Y
Y
Mase
K
K
Dai
Y
Y
Noguchi
M
M
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D019175:DNA Methylation; D004391:Dust / Q000009:adverse effects / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011009:Pneumoconiosis / Q000209:etiology / Q000378:metabolism*; D016133:Polymerase Chain Reaction
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004391:Dust