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Hypermethylation of FHIT as a prognostic marker in nonsmall cell lung carcinoma
Version of Record online: 25 FEB 2004
Copyright © 2004 American Cancer Society
Volume 100, Issue 7, pages 1472–1477, 1 April 2004
How to Cite
Maruyama, R., Sugio, K., Yoshino, I., Maehara, Y. and Gazdar, A. F. (2004), Hypermethylation of FHIT as a prognostic marker in nonsmall cell lung carcinoma. Cancer, 100: 1472–1477. doi: 10.1002/cncr.20144
- Issue online: 18 MAR 2004
- Version of Record online: 25 FEB 2004
- Manuscript Accepted: 13 JAN 2004
- Manuscript Revised: 6 JAN 2004
- Manuscript Received: 10 NOV 2003
- fragile histidine triad;
- promoter methylation;
- nonsmall cell lung carcinoma
Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC).
The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction.
The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RARβ) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6-methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001).
The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC. Cancer 2004;100:1472–7. © 2004 American Cancer Society.