Clinicopathologic significance of telomerase activity and hTERT mRNA expression in non-small cell lung cancer

Hara, Hidenori; Yamashita, Kazuya; Shinada, Jun; Yoshimura, Hirokuni; Kameya, Toru

doi:10.1016/s0169-5002(01)00244-6

Cited by 52 publications

(54 citation statements)

References 22 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%

“…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: Introductionmentioning

confidence: 99%

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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“…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). Some studies have associated overexpression with poor prognosis Hara et al, 2001;Marchetti et al, 2002;Hsu et al, 2004), while others have failed to do so (Wu et al, 2003).…”

Section: Discussionmentioning

confidence: 81%

“…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). Some studies have associated overexpression with poor prognosis Hara et al, 2001;Marchetti et al, 2002;Hsu et al, 2004), while others have failed to do so (Wu et al, 2003). One possible explanation is that hTERT mRNA has six known splice variants, but only the full-length transcript is functional.…”

Section: Discussionmentioning

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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“…15 High telomerase activity in tumor cells is one of the hallmarks of their 'immortality' and it is active in most human malignancies including lung, liver, gastric, breast, bladder and prostate cancers. 14,[16][17][18][19][20][21] TERT is the catalytic subunit of telomerase, and it is also a rate-limiting determinant of the enzymatic activity of human telomerase. 21 It has been shown that TERT is expressed at high levels in malignant tumors and tumor cell lines but is absent in normal postmitotic tissues.…”

Section: Introductionmentioning

confidence: 99%

Telomerase-dependent oncolytic adenovirus for cancer treatment

et al. 2003

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Conditionally replicative adenovirus (CRAD) is an attractive anticancer agent as it can selectively replicate in tumor cells. Expression of telomerase reverse transcriptase (TERT) is a unique tumor cell characteristic, being absent in normal postmitotic cells. Thus, we constructed a TERT promoter regulated CRAD for tumor-specific oncolysis by replacing the endogenous adenovirus E1A promoter with that of human TERT (Adv-TERTp-E1A). We showed that its replication was severely attenuated in TERT-negative cells, but that it replicated almost as efficiently as wild-type adenovirus in TERT-positive cells. Accordingly, Adv-TERTp-E1A conferred cytopathicity to TERT-positive, but not TERT-negative, cells. In vivo replication of Adv-TERTp-E1A after local administration into a xenograft model of human hepatocellular carcinoma in nude mice was demonstrated by an increase in adenovirus titers in tumor extracts by several orders of magnitude between 6 h and 3 days postvector injection. Furthermore, significant inhibition of tumor growth with substantial necrotic tumor areas staining positively for adenovirus was observed with Adv-TERTp-E1A, but not with a control replication-deficient adenovirus. There was also the absence of hepatotoxicity in tumor-bearing animals after intratumoral delivery of the CRAD. The results indicate that the TERT promoter-driven CRAD is capable of tumorselective replication and oncolysis in vitro and in vivo, and can be utilized as an adjuvant treatment agent for cancer.

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Clinicopathologic significance of telomerase activity and hTERT mRNA expression in non-small cell lung cancer

Cited by 52 publications

References 22 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

Telomerase-dependent oncolytic adenovirus for cancer treatment

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