Relevance of urine telomerase in the diagnosis of bladder cancer.
BACKGROUND
The identification of new molecular markers is one of the most challenging goals for the early detection of bladder cancer because available noninvasive methods have neither sufficient sensitivity nor specificity to be acceptable for routine use.


OBJECTIVE
To develop a relatively simple, inexpensive, and accurate test that measures telomerase activity in voided urine to apply to large-scale screening programs for bladder cancer detection.


METHODS
Case-control study conducted in 218 men (84 healthy individuals and 134 patients at first diagnosis of histologically confirmed bladder cancer), frequency matched by age and recruited between March 2003 and November 2004 in Italy. Urine telomerase activity was determined using a highly sensitive telomeric repeat amplification protocol (TRAP) assay. Urine samples were processed for cytological diagnosis and TRAP assay. The diagnosis of bladder cancer was based on bioptic and cystoscopic examinations. The performance of the TRAP assay to detect urine telomerase activity was compared with urine cytology as an aid to early cancer detection. Quantification of urine telomerase activity was conducted in a blinded manner.


METHODS
Sensitivity and specificity of TRAP to detect bladder cancer.


RESULTS
Using a 50 arbitrary enzymatic unit cutoff value, we validated the results obtained in the pilot study. In the overall series, sensitivity was 90% (95% confidence interval [CI], 83%-94%) and specificity was 88% (95% CI, 79%-93%). Specificity increased to 94% (95% CI, 85%-98%) for individuals aged 75 years or younger. The same predictive capacity of telomerase activity levels was observed for patients with low-grade tumors or with negative cytology results.


CONCLUSIONS
The present validation study demonstrated the ability of urine telomerase activity levels to accurately detect the presence of bladder tumors in men. This test represents a potentially useful noninvasive diagnostic innovation for bladder cancer detection in high-risk groups such as habitual smokers or in symptomatic patients.
Sanchini
Maria Aurora
MA
Division of Oncology and Diagnostics, Morgagni-Pierantoni Hospital, Forlì, Italy.
Gunelli
Roberta
R
Nanni
Oriana
O
Bravaccini
Sara
S
Fabbri
Carla
C
Sermasi
Alice
A
Bercovich
Eduard
E
Ravaioli
Alberto
A
Amadori
Dino
D
Calistri
Daniele
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000652:urine; D014556:Urine / Q000166:cytology
D014408:Biomarkers, Tumor; D019098:Telomerase