title: Telomere instability in papillary bladder urothelial carcinomas: Comparison with grading and risk of recurrence.
abstract: BACKGROUND
  Shortening of telomere is associated with cellular senescence and cancer. This study aims to investigate the relationship between tumor grade and recurrence in relation to telomere length (TL), telomerase activity (TA) and telomere-binding proteins expression (TBPs) in patients with non-muscle invasive bladder cancer (NMIBC).
  
  
  METHODS
  Tumor/healthy tissues were collected from 58 patients (35 with and 23 without NMIBC). Cystoscopy was performed at 3, 6 and 12 months to determine recurrence. Tumor grades and recurrence were correlated with TL, TA and TBPs using the Kruskal-Wallis non-parametric test. Results were considered significant at P < 0.05.
  
  
  RESULTS
  Histological evaluation indicated 15 patients (42.9%) with high-grade (HG) and 20 patients (57.1%) with low-grade (LG) NMIBC. TL, TA and TBPs were found to be significantly different in tumors as compared with controls. A significant (P < 0.05) difference in the expression of TBPs was observed in the disease-free mucosa of cancer patients as compared with HG and LG tumors. In the follow-up, a total of 11 tumor recurrences were observed; among these eight recurrences were observed in patients with HG tumors and three in patients with LG tumors. TL,  Human telomerase reverse transcriptase (hTERT) (that represents TA) and poly (ADP-ribose) polymerase 1 (PARP-1) in tumor samples and telomeric repeat binding factors TRF1, TRF2 and tankyrase (TANK) in normal mucosa obtained from the tumor group were respectively found to exhibit a positive and negative association with the risk of recurrence.
  
  
  CONCLUSIONS
  Our study demonstrates that TL, TA and TBPs are altered in tumors and non-cancerous mucosa in patients with papillary urothelial NMIBC. Further studies are warranted to identify their suitability as a potential biomarker.
authors.affiliation: Department of Urology, University of Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mucciardi
authors.affiliation: Department of Urology, University of Messina, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gali'
authors.affiliation: Department of Human Pathology, University of Messina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Barresi
authors.affiliation: Department of Economics Statistics Mathematics and Sociology, University of Messina, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mucciardi
authors.affiliation: Department of Neuroscience Psychiatrics and Anesthesiology Sciences, University of Messina, Italy.
authors.forename: M'Hammemd
authors.initials: M
authors.lastname: Aguennouz
authors.affiliation: Department of Urology, University of Messina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Inferrera
authors.affiliation: Department of Urology, University of Messina, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Magno
keywords: Bladder cancer; non-muscle invasive bladder cancer; telomerase; telomere; telomere-binding proteins; urothelial carcinomas
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