Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients

Abstract

Background: Ataxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients. Patients and methods: The ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. Results: Reduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27-4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16-6.32), and larger tumor (T3/T4, HRR = 2.21; 95% CI 1.10-4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05-20.66) or with lower ATM and T3/T4 tumor (HRR = 5.23; 95% CI 2.04-13.40) exhibited the poorest outcome. Conclusion: The expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.