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Carcinogenesis Advance Access published online on September 11, 2003
Carcinogenesis, doi:10.1093/carcin/bgg169
© 2003 by Oxford University Press
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© 2003 Oxford University Press

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

Hypermethylation of p16INK4a in Chinese lung cancer patients: biological and clinical implications

Yong Liu 1, Qian An 1, Ling Li 1, Dechao Zhang 1, Jinfeng Huang 1, Xiaoli Feng 1, Shujun Cheng 1, and Yanning Gao 2*

1 Department of Chemical Etiology and Carcinogenesis, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, P. R. China
2 Cancer Institute, Peking Union Medical College & Chinese Academy of Medical Sciences, PO Box 2258, Beijing 100021, P. R. China

* Corresponding author. E-mail: yngao{at}pubem.cicams.ac.cn.

Received 29 July 2003 ; revised 22 May 2003 ; accepted 29 August 2003

Abstract

Promoter hypermethylation of the p16INK4a gene was investigated in 111 cases of tumor tissue, as well as in 136 circulating plasma and 95 sputum samples from Chinese patients with primary lung cancer, using a modified protocol of semi-nested methylation-specific-PCR (MSP). The results showed hypermethylated p16 sequence in 80.2% of tumor tissues and frequencies of 75.7% and 74.7% in plasma and sputum specimens, respectively. Among the patients, 50 cases of matched plasma, sputum and tumor tissue from the same individual were analyzed. Of these, hypermethylation of the p16 promoter was detected in 84.0% of the tumor tissues, with frequencies of 72.0% and 76.0% in the corresponding plasma and sputum, respectively. Notably, only patients whose tumor tissue showed hypermethylation of p16 exhibited the same aberrant methylation in their sputum and/or plasma. Hypermethylation of p16 in sputum and plasma samples may provide a more sensitive approach to molecular diagnosis of lung cancer than relying on conventional cytological analysis. Our data show that a combination of cytological analysis of sputum and examination of p16 hypermethylation in sputum and plasma identified 92.0% (46/50) of the lung cancer patients studied, offering an effective means of early detection of lung cancer.


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