Prognostic Impact of Telomerase Activity in Non-Small Cell Lung Cancers

Taga, Satoshi; Osaki, Toshihiro; Ohgami, Akira; Imoto, Hideyuki; Yasumoto, Kosei

doi:10.1097/00000658-199911000-00015

Cited by 72 publications

(47 citation statements)

References 31 publications

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“…In line with previous studies we found that both the proportion of hTERT-positive samples and hTERT mRNA levels were higher in tumour samples than in paired normal lung samples of lung cancer patients (19,20,22,(26)(27)(28)(29)(30). However, despite the fact that we examined material of a large cohort of patients and found an association between clinical stage and hTERT mRNA positivity in tumour tissue, we were unable to confirm a previously reported association between RT-PCR detected elevated hTERT mRNA levels of tumour samples and a decreased disease-free survival (19,20,22).…”

Section: Discussionsupporting

confidence: 92%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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“…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). The clinical significance of increased hTERT gene copy number has not been investigated.…”

mentioning

confidence: 99%

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

et al. 2006

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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 (Po0.001) 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 ¼ 0.03). Overexpression was significantly associated with amplification (P ¼ 0.03), especially in adenocarcinoma. The hTERT gene amplification was prognostic for shorter recurrence-free survival (hazard ratio ¼ 2.16, P ¼ 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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“…Whereas normal colonic crypt epithelial cells exhibiting stem cells properties express very weak telomerase activity within the proliferative zone of the crypt (Tahara et al, 1995;Kolquist et al, 1998), evidences have been accumulated over years to suggest that telomerase is up-regulated as a function of increased tumour cell invasion, tumour progression, and metastatic potential in colon cancer Yoshida et al, 1999). Similarly, at the tumour site, telomerase activity has been shown to be an important prognostic factor for NSCLC (Albanell et al, 1997;Marchetti et al, 1999;Taga et al, 1999). Whereas we never found telomerase activity in HEC samples from 30/30 healthy donors, telomerase was expressed in more than 72% of the patients with advanced carcinoma involved in this study.…”

Section: Discussionmentioning

confidence: 99%

Detection of circulating carcinoma cells by telomerase activity

et al. 2001

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Summary Telomerase has been shown to be a marker of epithelial cancer cells. We developed a method that allows the detection of circulating carcinoma cells in the blood of cancer patients. Circulating epithelial cells are harvested from peripheral blood mononuclear cells by immunomagnetic separation using BerEP4-coated beads. A telomeric repeat amplification protocol (TRAP)-ELISA is then used to measure telomerase in harvested epithelial cells. This method is specific and sensitive as demonstrated by experiments using BerEP4-positive and negative cell lines. Whereas we never found telomerase activity in harvested epithelial cells (HEC) samples from 30/30 healthy donors, we have detected telomerase activity in HEC from 11/15 (73%) patients with stage IIIB or IV non-small cell lung cancer (NSCLC) patients and from 8/11 (72%) stage C or D (Dukes classification) colon cancer patients. This non-invasive method could be of great value as a diagnostic or prognostic marker, or for monitoring cancer progression.

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Prognostic Impact of Telomerase Activity in Non-Small Cell Lung Cancers

Cited by 72 publications

References 31 publications

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

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

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

Detection of circulating carcinoma cells by telomerase activity

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