Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours

Abstract

Human telomerase reverse transcriptase is a ribonucleoprotein that synthesises telomeric sequences, which decrease at each cell division. In cancer cells, its activity is linked to telomere maintenance leading to unlimited cellular proliferation and immortality. To evaluate the prognostic value of the catalytic subunit telomerase reverse transcriptase (hTERT), we analysed its expression by immunohistochemistry in 122 formalin-fixed lung tumours including 42 squamous cell carcinoma (SCC), 43 adenocarcinoma (ADC), 19 basaloid carcinoma (BC) and 18 small-cell lung carcinoma (SCLC) in comparison with detection of hTERT mRNA by in situ hybridisation and relative telomerase activity by TRAP assay in a subset of tumours. We observed a high concordance between hTERT protein expression and detection of hTERT mRNA and telomerase activity. Telomerase expression varied according to histology (P ¼ 0.0002) being significantly lower in ADC than in SCC, BC and SCLC (Po0.0001). Adenocarcinoma and SCC exhibited either a nuclear or a nucleolar staining in contrast with a diffuse nuclear staining observed in most BC and all SCLC (P ¼ 0.01). In stage I NSCLC telomerase expression was lower than in other stages (P ¼ 0.04), and a nucleolar staining was correlated with a short survival (P ¼ 0.03). We concluded that telomerase expression and pattern are distinctive among histopathological classes of lung cancer and convey prognostic influence.

Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

“…In patients with surgically-treated early-stage lung cancer a correlation has been found between a poor prognosis and detection in tumour tissue of either elevated hTERT expression [by RT-PCR (19)(20)(21)(22), immunohistochemistry (23) or ISH (24,25)] or telomerase activity (26)(27)(28)(29). However, data on this topic are not consistent since other studies failed to reveal a correlation between hTERT expression and (diseasefree) survival (28,30,31).…”

“…Studies on the potentially prognostic value of telomerase activity or hTERT expression in tumours of surgically treated lung cancer patients have, however, yielded conflicting results (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). The possibility that the level of hTERT mRNA and telomerase activity, rather than detectability of these parameters could have a predictive value might be one of the reasons for these discordant findings.…”

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

“…Such an association has been reported in mISH (Kumaki et al, 2001;Wang et al, 2002;Fujita et al, 2003;Lantuejoul et al, 2004) and immunohistochemistry studies (Kumaki et al, 2001;Toomey et al, 2001;Lantuejoul et al, 2004). In contrast, the prognostic value of hTERT mRNA expression assayed by RT -qPCR has been inconsistent Hara et al, 2001;Marchetti et al, 2002;Wu et al, 2003;Hsu et al, 2004).…”

“…Activations of the hTERT or ALT pathways are obligate for senescence bypass and for neoplastic transformation of normal cells (Newbold, 2002). Telomerase activity and/or hTERT expression are increased in cancers and are prognostic factors in various cancer types (Harada et al, 1999;Bieche et al, 2000;Lee et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Krams et al, 2003;Ohali et al, 2003;Tchirkov et al, 2003;Lantuejoul et al, 2004). However, the clinical impact of hTERT expression or activity in non-small-cell lung cancer (NSCLC) remains controversial (Albanell et al, 1997;Taga et al, 1999;Hirashima et al, 2000;Komiya et al, 2000;Toomey et al, 2001;Marchetti et al, 2002;Wang et al, 2002;Fujita et al, 2003;Wu et al, 2003;Hsu et al, 2004;Lantuejoul et al, 2004).…”

TERT Promoter Mutations and Tert Expression in Early-Stage (T1N0M0) Non-Small Cell Lung Cancer (NSCLC)

“…Moreover, high telomerase expression and activity have been found to be associated with both high-grade tumors and a more advanced clinical stage in lung cancers [33,34]. Our series is mainly composed of moderately differentiated tumors and a low number both of well differentiated cases and poorly differentiated ones, which inhibited our ability to correlate telomerase expression and tumor grade.…”