Paolo Boscolo-Rizzo1, Enrica Rampazzo2, Egle Perissinotto3, Maria Assunta Piano2, Silvia Giunco4, Lorena Baboci2, Giacomo Spinato5, Roberto Spinato6, Giancarlo Tirelli5, Maria Cristina Da Mosto1, Annarosa Del Mistro4, Anita De Rossi7. 1. Section of Otolaryngology and Regional Center for Head and Neck Cancer, Department of Neurosciences, University of Padova, Treviso, Italy. 2. Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. 3. Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiological Thoracic and Vascular Sciences, University of Padova, Padova, Italy. 4. Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto - IRCCS, Padova, Italy. 5. Head and Neck Department, University of Trieste, Trieste, Italy. 6. Otolaryngology Unit, Ospedale dell'Angelo, Venezia, Italy. 7. 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.
Abstract
OBJECTIVES: 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). MATERIALS AND 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.
OBJECTIVES: 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). MATERIALS AND 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.
Keywords:
Field cancerization; Head and neck cancer; Human papilloma virus; Local relapse; Molecular biology; Survival; TERT; Telomerase reverse transcriptase; Telomeres
Authors: Martine Froukje van der Kamp; Gyorgy Bela Halmos; Victor Guryev; Peter Laszlo Horvatovich; Ed Schuuring; Bernardus Franciscus Augustinus Maria van der Laan; Bert van der Vegt; Boudewijn Evert Christiaan Plaat; Cornelia Johanna Verhoeven Journal: Cell Oncol (Dordr) Date: 2022-01-11 Impact factor: 6.730
Authors: G Tirelli; S Zacchigna; F Boscolo Nata; E Quatela; R Di Lenarda; M Piovesana Journal: Eur Arch Otorhinolaryngol Date: 2016-08-04 Impact factor: 2.503
Authors: Paolo Boscolo-Rizzo; Silvia Giunco; Enrica Rampazzo; Martina Brutti; Giacomo Spinato; Anna Menegaldo; Marco Stellin; Monica Mantovani; Luigia Bandolin; Marco Rossi; Annarosa Del Mistro; Giancarlo Tirelli; Angelo Paolo Dei Tos; Angela Guerriero; Monia Niero; Maria Cristina Da Mosto; Jerry Polesel; Anita De Rossi Journal: J Cancer Res Clin Oncol Date: 2020-01-20 Impact factor: 4.553