Diagnosis of bladder cancer using telomerase activity in voided urine.
OBJECTIVE
Telomerase is an essential enzyme for cellular immortality and tumorigenesis. Reactivation of telomerase is associated with many primary cancers. We evaluated the accuracy of a modified immunodiagnostic technique based on the telomeric repeat amplification protocol (TRAP) assay, by semi-quantitative measurement of telomerase activity in exfoliated urothelial cells in voided urine from patients with bladder cancer.


METHODS
Telomerase activity was assayed in centrifuged urine cell pellets from 17 bladder cancer patients and from 32 patients with benign bladder diseases. Each specimen was collected from a 50-mL sample of single voided urine obtained before surgery, and telomerase activity was detected using a telomerase polymerase chain reaction and enzyme-linked immunosorbent assay (PCR-ELISA) protocol. Results of pathologic study, urine cytologic examination, and urine telomerase activity were determined independently.


RESULTS
The cut-off value for relative telomerase activity was set at 0.059, which provided an optimal diagnostic accuracy of 88% (n = 49). At this cut-off value, the sensitivity and specificity for urine telomerase in bladder cancer were 82% (n = 17) and 91% (n = 32), respectively. Telomerase activity was found in 11 low-grade tumors and six high-grade tumors, whereas negative results for telomerase activity were found in urothelial cells of patients with inguinal hernia, urinary stones, acute urinary tract infection, or chronic cystitis. Only five cytology samples from the same patients were positive for bladder cancer. The difference in these two detection rates was significant (p = 0.002).


CONCLUSIONS
The results of this study indicate that the measurement of telomerase activity from voided urine using our modified semi-quantitative PCR-ELISA technique may help provide earlier diagnosis of bladder cancer and earlier postoperative indication of recurrence.
Cheng
C W
CW
Graduate Institute of Pharmaceutical Sciences, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei, Taiwan.
Chueh
S C
SC
Chern
H D
HD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*; D014556:Urine / Q000166:cytology*; D019459:Urothelium / Q000201:enzymology*
D014408:Biomarkers, Tumor; D019098:Telomerase