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

Br J Cancer. 2006 May 22;94(10):1452-9. doi: 10.1038/sj.bjc.6603110.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase / genetics*

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • RNA, Messenger
  • Telomerase