title: Telomere shortening in mucosa surrounding the tumor: biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  The aim of the present study was to investigate the pattern of telomere length and telomerase expression in cancer tissues and the surrounding mucosa (SM), as markers of field cancerization and clinical outcome in patients successfully treated for with head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  This investigation was a prospective cohort study. Telomere length and levels of telomerase reverse transcriptase (TERT) transcripts were quantified by real-time PCR in cancer tissues and SM from 139 and 90 patients with HNSCC, respectively.
  
  
  RESULTS
  No correlation was found between age and telomere length in SM. Patients with short telomeres in SM had a higher risk of mucosal failure (adjusted HR=4.29). Patients with high TERT levels in cancer tissues had a higher risk of regional failure (HR=2.88), distant failure (HR=7.27), worse disease-specific survival (HR for related death=2.62) but not mucosal failure. High-risk patients having both short telomeres in SM and high levels of TERT in cancer showed a significantly lower overall survival (HR=2.46).
  
  
  CONCLUSIONS
  Overall these findings suggest that telomere shortening in SM is a marker of field cancerization and may precede reactivation of TERT. Short telomeres in SM are strongly prognostic of mucosal failure, whereas TERT levels in cancer tissues increase with the aggressiveness of the disease and are prognostic of tumor spread.
authors.affiliation: Section of Otolaryngology and Regional Center for Head and Neck Cancer, Department of Neurosciences, University of Padova, Treviso, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Boscolo-Rizzo
authors.affiliation: Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Rampazzo
authors.affiliation: Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiological Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
authors.forename: Egle
authors.initials: E
authors.lastname: Perissinotto
authors.affiliation: Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Maria Assunta
authors.initials: MA
authors.lastname: Piano
authors.affiliation: Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto - IRCCS, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giunco
authors.affiliation: Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Baboci
authors.affiliation: Head and Neck Department, University of Trieste, Trieste, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Spinato
authors.affiliation: Otolaryngology Unit, Ospedale dell'Angelo, Venezia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Spinato
authors.affiliation: Head and Neck Department, University of Trieste, Trieste, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tirelli
authors.affiliation: Section of Otolaryngology and Regional Center for Head and Neck Cancer, Department of Neurosciences, University of Padova, Treviso, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Da Mosto
authors.affiliation: Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto - IRCCS, Padova, Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Del Mistro
authors.affiliation: Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto - IRCCS, Padova, Italy. Electronic address: anita.derossi@unipd.it.
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015374:Biosensing Techniques; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009092:Mucous Membrane / Q000378:metabolism*; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism; D016615:Telomere
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase
keywords: Field cancerization; Head and neck cancer; Human papilloma virus; Local relapse; Molecular biology; Survival; TERT; Telomerase reverse transcriptase; Telomeres