Predictive and prognostic significance of telomerase levels/telomere length in tissues and peripheral blood in head and neck squamous cell carcinoma

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Paolo Boscolo-Rizzo
Enrica Rampazzo
Jerry Polesel
Silvia Giunco
Anna Menegaldo
Monica Mantovani
Marco Stellin
Luigia Bandolin
Giacomo Spinato
Annarosa Del Mistro
Daniele Borsetto
Jonathan Fussey
Giancarlo Tirelli
Maria Cristina Da Mosto
Anita De Rossi
机构
[1] University of Padova,Department of Neurosciences, Section of Otolaryngology and Regional Centre for Head and Neck Cancer
[2] University of Padova,Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology
[3] Unit of Cancer Epidemiology,Immunology and Molecular Oncology Unit
[4] Centro di Riferimento Oncologico di Aviano (CRO) IRCCS,Department of ENT, Addenbrooke’s Hospital
[5] Istituto Oncologico Veneto IOV-IRCCS,Department of Otolaryngology
[6] Cambridge University Hospitals,Head and Neck Department, Hospital of Cattinara
[7] Royal Devon and Exeter Hospital,undefined
[8] University of Trieste,undefined
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A growing body of evidence indicates that the expression of TERT, the catalytic subunit of telomerase, is a biological marker of progression in several cancers. We investigated the predictive and prognostic role of TERT levels and telomere length in tissues and peripheral blood in patients with head and neck squamous cell carcinoma (HNSCC). High TERT levels in cancer tissues were independently associated with worse response to therapy (odds ratio [OR]:6.26), regional failure (hazard ratio [HR]:5.75), progression (HR:2.12), and death (HR:3.53). Longer telomeres in the mucosa surrounding the tumor (SM) were independently associated with a lower risk of mucosal failure (HR:0.39). While telomere length in peripheral blood mononuclear cells (PBMC) significantly decreased with age, no correlation was found between age and telomere length in SM. No associations were found between TERT levels in plasma and telomere length in PBMC and the prognostic variables. High levels of TERT transcripts in cancer cells represent a reliable prognostic marker for identifying HNSCC patients with risk of progression. The altered relationship of telomere length to age in SM compared with PBMC suggests that in a subset of cases the phenotypically normal SM constitutes an acquired telomere-shortened epithelial field prone to genetic instability.
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