Tankyrase-1 mRNA expression in bladder cancer and paired urine sediment: preliminary experience.

Background: The enzyme tankyrase-1 (TNKS-1), a member of the growing family of poly(ADP-ribose) polymerases (PARPs), was identified as a component of the human telomeric complex. PARPs catalyze the formation of long chains of poly(ADP-ribose) onto protein acceptors using NADq as a substrate. TNKS-1 interacts with the telomeric DNA-binding protein TTAGGG repeat-binding factor 1 (TRF1), which is a negative regulator of telomere length. TNKS-1 is a positive regulator of telomere elongation and its activity appears to be upregulated in some human cancers. Methods: We evaluated for the first time TNKS-1 mRNA expression by real time RT-PCR in tumor tis- sue, paired normal mucosa and urine sediment in patients with transitional cell carcinoma (TCC) of the bladder. Samples were collected from 41 consecutive patients, 20 with non-muscle-invasive (pTa-pT1) and 21 with muscle-invasive (GpT2) bladder TCC. Results obtained in urine sediment were compared with those from 40 healthy subjects matched for age and sex. Results: In pTa-pT1 tumor tissues, TNKS-1 mRNA lev- els were significantly higher than in GpT2 patients (p-0.0001). In urine sediment from TCC patients, independent of tumor stage, TNKS-1 mRNA levels were significantly higher than in healthy controls, with maximal levels in GpT2 patients. In particular, TNKS-1 mRNA levels in urine were elevated in 31/41 patients with a sensitivity of 81% in GpT2 tumors and 65% in pTa-pT1 TCC. Of patients with pTa-pT1 tumors, 11 had a recurrence within 18 months after initial transurethral resection. In these patients, urine levels of TNKS-1 mRNA were higher than in non- relapsing patients (ps0.038). Conclusions: In this preliminary study, TNKS-1 mRNA in urine sediment from patients with bladder TCC cor- related with tumor stage, and higher preoperative lev- els were associated with increased risk of early recurrence.