TY - JOUR
T1 - Telomere shortening in mucosa surrounding the tumor
T2 - Biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma
AU - Boscolo-Rizzo, Paolo
AU - Rampazzo, Enrica
AU - Perissinotto, Egle
AU - Piano, Maria Assunta
AU - Giunco, Silvia
AU - Baboci, Lorena
AU - Spinato, Giacomo
AU - Spinato, Roberto
AU - Tirelli, Giancarlo
AU - Da Mosto, Maria Cristina
AU - Del Mistro, Annarosa
AU - De Rossi, Anita
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Field cancerization
KW - Head and neck cancer
KW - Human papilloma virus
KW - Local relapse
KW - Molecular biology
KW - Survival
KW - Telomerase reverse transcriptase
KW - Telomeres
KW - TERT
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UR - http://www.scopus.com/inward/citedby.url?scp=84933670812&partnerID=8YFLogxK
U2 - 10.1016/j.oraloncology.2015.02.100
DO - 10.1016/j.oraloncology.2015.02.100
M3 - Article
C2 - 25771075
AN - SCOPUS:84933670812
SN - 1368-8375
VL - 51
SP - 500
EP - 507
JO - Oral Oncology
JF - Oral Oncology
IS - 5
ER -