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Comparative Study
. 2006 May 22;94(10):1452-9.
doi: 10.1038/sj.bjc.6603110.

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

C-Q Zhu  1 , J-C Cutz, N Liu, D Lau, F A Shepherd, J A Squire, M-S Tsao
Affiliations
Comparative Study

Amplification of telomerase (hTERT) gene is a poor prognostic marker in non-small-cell lung cancer

C-Q Zhu et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
The distribution of hTERT gene copy number and mRNA expression levels according to tissue and tumour type. N, normal lung tissue; ADC, adenocarcinoma, SQCC, squamous cell carcinoma; LCC, large-cell lung carcinoma.
Figure 2
Figure 2
Kaplan–Meier survival plots. (A) Recurrence-free survival (RFS) according to hTERT gene copy. (B) Overall survival (OS) according to hTERT gene copy. (C) RFS according to expression levels of hTERT mRNA expression levels. (D) Overall survival according to hTERT mRNA expression levels.
Figure 3
Figure 3
Representative fluorescent in situ hybridisation (FISH) images. (A) A tumour with diploid genotype showing most tumour cell nuclei containing two green signals (hTERT, 5p15.33) and two red signals (control locus, 5q31). (B) A polysomy tumour showing several signals of both the hTERT and 5q; (C) Tumour with high-level amplification with their nuclei containing 10–30 hTERT signals and two or more 5q signals.
See this image and copyright information in PMC

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