1. ¹Division of Applied Molecular Oncology, Ontario Cancer Institute, Ontario, Toranto, Canada
2. ²Department of Pathology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
3. ³Division of Hematology and Medical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
4. ⁴Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5G 2M9
5. ⁵Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 2M9
6. ⁶Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2M9

Correspondence: Dr M-S Tsao, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. E-mail: Ming.Tsao@uhn.on.ca

Received 12 December 2005; Revised 20 March 2006; Accepted 20 March 2006; Published online 25 April 2006.

Abstract

Telomerase reactivation is a hallmark of human carcinogenesis. Increased telomerase activity may result from gene amplification and/or overexpression. This study evaluates the prognostic value of hTERT gene amplification and mRNA overexpression in 144 resectable non-small-cell lung cancer (NSCLC) specimens. The hTERT gene copy number was assessed by quantitative polymerase chain reaction (qPCR) on laser-capture microdissected tumour cells of 81 tumours, and by fluorescence in situ hybridisation (FISH) on a subset of 59 tumours. hTERT mRNA level was determined by reverse transcription (RT)–qPCR in 130 tumours. In total, 57% of (46 out of 81) primary NSCLC specimens demonstrated hTERT amplification, which was significantly more common (P<0.001) in adenocarcinoma (30 out of 40) than in squamous cell carcinoma (13 out of 37). The hTERT mRNA overexpression was noted in 74% (94 out of 130) of tumours; it was more frequent in squamous cell than in adenocarcinoma (87 vs 68%, P=0.03). Overexpression was significantly associated with amplification (P=0.03), especially in adenocarcinoma. The hTERT gene amplification was prognostic for shorter recurrence-free survival (hazard ratio=2.16, P=0.03). These data indicate that gene amplification is an important mechanism for hTERT overexpression in lung adenocarcinoma and is an independent poor prognostic marker for disease-free survival in NSCLC.