Expression of telomerase genes in thyroid carcinoma

Hoang‐Vu, Cuong; Boltze, Carsten; Gimm, Oliver; Poremba, Christopher; Dockhorn‐Dworniczak, Barbara; Köhrle, Josef; Rath, Friedrich-Wilhelm; Dralle, Henning

doi:10.3892/ijo.21.2.265

Cited by 21 publications

(27 citation statements)

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“…All further hTERT scores in the tumor margin and tumor distant tissues (Table V) correlate in varying degrees with telomerase activity. We ascertained in our study, as had other authors in regard to diverse tumors (21,52,(54)(55)(56)(57), that the absence of telomerase activity [under 150 mOD (13-15)] does not always coincide with the absence of hTERT expression and vice versa. Shay et al (58) did not always observe a correlation between the levels of telomerase and those of hTERT expression, while Etheridge et al (59) found a strong correlation between telomerase activity and hTERT expression.…”

Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 60%

“…This antibody is recommended by the manufacturer for immunofluorescence and has been reported by Wei and Younes (62), Hoang-Vu et al (54) and Boltze et al (80) to give good proof of hTERT in a variety of different tumors. However, given the results we obtained, we abandoned its further use and did not report in detail the results obtained with it.…”

Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 96%

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Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

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Abstract.In previous studies we demonstrated telomerase activity in frozen tissue from head and neck squamous cell carcinoma (HNSCC) and their tumor-free tumor margins. In the present study frozen sections from the same tissues were examined for in situ presence of hTERT. In preliminary investigations we established that the most suitable method of tissue preparation was fixation in acetone and methanol followed by steaming and visualization by APAAP. Most of the assays involved eleven anti-hTERT antibodies and were supplemented with the inclusion of antibodies Ki-67, antinucleolin and CD45. hTERT expression was investigated in the tissues of 61 patients with HNSCC and 37 patients without tumor. Semi-quantitative immunoreactive scores were correlated with telomerase activity. We examined the prognostic significance of hTERT expression with Kaplan-Meier curves and tested the immunological specificity of the antibodies by immunoabsorption with two hTERT peptides and a nucleolin peptide. Nuclear staining of satisfactory distribution and intensity was achieved in seven anti-hTERT antibodies both in the carcinomas and in the squamous epithelia of the tumor resection margins and in the control tissues. Proof of hTERT did not differ from telomerase activity. The telomerase activity demonstrated in tumor-free resection margins and in control tissues did, however, correlate with lymphocytic-monocytic infiltration (CD45 expression). This telomerase activity might be related to nuclear hTERT expression in the squamous epithelium, given that the hTERT score values in the connective tissue tended to be negative. The prognostic significance of hTERT expression demonstrated on paraffin sections from different tumor localizations was not confirmed for the frozen sections of patients with HNSCC. The hTERT specificity of the monoclonal NCL-L-hTERT, whose use as an antibody against hTERT has been questioned, was reexamined with immunohistochemical methods, but the intensity of its immunoabsorption with the nucleolin peptide did not exceed that observed in the other anti-hTERT antibodies.

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Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 60%

Section: Correlation Of Htert Score Values and Telomerase Activity Inmentioning

confidence: 96%

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Fabricius

Kruse-Boitschenko²,

Khoury³

et al. 2009

Int J Oncol

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“…Some authors described so-called solid cell nests (SCNs) of the thyroid, which are embryonic remnants of the ultimobranchial body: these may represent the thyroid stem cell pool, as they express several stem cell markers, namely telomerase (Reis-Filho et al 2003, Preto et al 2004. Thyroid cancer displays less frequent telomerase activation than other cancer types; telomerase activity has been found in 48% of papillary thyroid carcinomas (PTC), 71% of follicular thyroid carcinomas (FTC) and 78% of poorly differentiated and anaplastic thyroid carcinomas (PDTC and ATC, respectively) (Aogi et al 1999, Saji et al 1999, Hoang-Vu et al 2002, Takano et al 2007.…”

Section: Tert Promoter Mutations In Thyroid Cancermentioning

confidence: 99%

TERT biology and function in cancer: beyond immortalisation

Pestana

Vinagre

Sobrinho-Simões

et al. 2017

Journal of Molecular Endocrinology

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Evasion of replicative senescence and proliferation without restriction, sometimes designated as immortalisation, is one of the hallmarks of cancer that may be attained through reactivation of telomerase in somatic cells. In contrast to most normal cells in which there is lack of telomerase activity, upregulation of TERT transcription/activity is detected in 80-90% of malignant tumours. In several types of cancer, there is a relationship between the presence of TERT promoter mutations, TERT mRNA expression and clinicopathological features, but the biological bridge between the occurrence of TERT promoter mutations and the aggressive/invasive features displayed by the tumours remains unidentified. We and others have associated the presence of TERT promoter mutations with metastisation/survival in several types of cancer. In follicular cell-derived thyroid cancer, such mutations are associated with worse prognostic features (age of patients, tumour size and tumour stage) as well as with distant metastases, worse response to treatment and poorer survival. In this review, we analyse the data reported in several studies that imply TERT transcription reactivation/activity with cell proliferation, tumour invasion and metastisation. A particular attention is given to the putative connections between TERT transcriptional reactivation and signalling pathways frequently altered in cancer, such as c-MYC, NF-κB and B-Catenin.

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“…58,59 Expression of hTR has previously been determined in many cancers and it generally does not correlate with hTERT expression levels. [60][61][62] Unlike hTERT, the expression of hTR does not predict the presence or amount of telomerase activity. 58,63 We have shown that hTR levels, in general, were increased in the CD34 þ cells from the majority of CML patients in all phases (however, two CP patients have hTR expression levels below the range of normal controls).…”

Section: Normal Haematopoietic Cd34mentioning

confidence: 99%

“…Similar observations have been made in many other malignancies including AML and thyroid cancer. 60,61 c-Myc positively regulates telomerase and a significant association between c-Myc over-expression and elevated hTERT expression has been demonstrated in several cancers. 25,64,65 We have shown that c-Myc expression levels were high in most patients in CP and decreased with disease progression falling below the levels observed in controls in the majority of BC patients.…”

Section: Normal Haematopoietic Cd34mentioning

confidence: 99%

hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia

et al. 2006

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Telomere shortening is associated with disease progression in chronic myeloid leukaemia (CML). To investigate the biology and regulation of telomerase in CML, we evaluated expression of the telomerase components, its regulators and several telomeric-associated proteins. Quantitative real-time-polymerase chain reaction (PCR) was used to compare gene expression in the CD34 þ /leukaemic blast cells of 22 CML patient samples to the CD34 þ cell population of healthy individuals. hTERT, the catalytic component of telomerase, was downregulated in eight of 12 chronic phase (CP) patients (P ¼ 0.0387). Furthermore, hTERT was significantly downregulated in two of three patients in accelerated phase (AP) and seven of seven patients in blast crisis (BC), P ¼ 0.0017. Expression of hTR and telomericassociated proteins TEP1, TRF1, TRF2, tankyrase and PinX1 was high in the majority of CP and AP patients. With the exceptions of TEP1 and hTR, expression of these factors was highest in CP and decreased during disease progression. Expression of c-Myc, a positive regulator of hTERT transcription, correlated with hTERT expression and decreased with disease progression, falling below control levels in BC. hTERT levels were increased in CP patients following successful treatment with imatinib, relative to untreated CP patients. We suggest that reduced hTERT expression directly causes the shortened telomeres observed in CML.

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Expression of telomerase genes in thyroid carcinoma

Cited by 21 publications

References 0 publications

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

Immunohistochemical determination of the appropriate anti-hTERT antibodies for in situ detection of telomerase activity in frozen sections of head and neck squamous cell carcinomas and tumor margin tissues

TERT biology and function in cancer: beyond immortalisation

hTERT, the catalytic component of telomerase, is downregulated in the haematopoietic stem cells of patients with chronic myeloid leukaemia

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