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Purpose: Telomerase reactivation is a hallmark of human cell carcinogenesis. Increased telomerase activity may result from gene amplification and/or overexpression. The present study evaluates the prognostic value of increased hTERT gene dosage and mRNA expression in early stage non-small cell lung cancer patients (NSCLC). Experimental Design: A total of 144 primary NSCLC tumor specimens were included in this study. The gene copy number of hTERT was assessed using the Quantitative-PCR (Q-PCR) after laser-captured microdissection (LCM) in 81 tumors. The hTERT mRNA expression levels were determined in 130 NSCLC tumors. Results: Fifty seven percent primary NSCLC showed gene copy number increases, which was more common in adenocarcinoma (AD, 30/40) than in squamous cell carcinoma (SQ, 13/37; p<0.001). The overexpression of hTERT was noted as 74 % (67.9% in AD and 86.8% in SQ; p=0.027). Gene copy number changes were significantly correlated with mRNA expression level (r=0.27, p=0.031). Stratified analysis showed that the correlation only existed in SQ (r=0.49, p=0.004). While hTERT overexpression was only associated with deceased overall survival time (p=0.031), hTERT gene copy number overrepresentation was associated with both shorter disease-free survival (p=0.008) and deceased overall survival time (p=0.024). Cox proportional hazards analysis showed that hTERT copy number overrepresentation was an independent prognostic marker (p=0.045) for disease-free survival and its overexpression was an independent prognostic marker for overall survival (p=0.025) in NSCLC. In addition, only the expression level was associated with tumor stage (p=0.027). Conclusion: Gene dosage is an important regulatory mechanism for hTERT gene overexpression in SQ and is an independent prognostic marker in resected NSCLC.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]