Relevance of Urine Telomerase in the Diagnosis of Bladder Cancer

CONTEXT 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, ine...

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Veröffentlicht in:JAMA : the journal of the American Medical Association 2005-10, Vol.294 (16), p.2052-2056
Hauptverfasser: Sanchini, Maria Aurora, Gunelli, Roberta, Nanni, Oriana, Bravaccini, Sara, Fabbri, Carla, Sermasi, Alice, Bercovich, Eduard, Ravaioli, Alberto, Amadori, Dino, Calistri, Daniele
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container_end_page 2056
container_issue 16
container_start_page 2052
container_title JAMA : the journal of the American Medical Association
container_volume 294
creator Sanchini, Maria Aurora
Gunelli, Roberta
Nanni, Oriana
Bravaccini, Sara
Fabbri, Carla
Sermasi, Alice
Bercovich, Eduard
Ravaioli, Alberto
Amadori, Dino
Calistri, Daniele
description CONTEXT 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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOME MEASURE 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.
doi_str_mv 10.1001/jama.294.16.2052
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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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOME MEASURE 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.</description><identifier>ISSN: 0098-7484</identifier><identifier>EISSN: 1538-3598</identifier><identifier>DOI: 10.1001/jama.294.16.2052</identifier><identifier>PMID: 16249419</identifier><identifier>CODEN: JAMAAP</identifier><language>eng</language><publisher>Chicago, IL: American Medical Association</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers, Tumor - urine ; Bladder cancer ; Cancer ; Case-Control Studies ; Excretory system ; General aspects ; Humans ; Male ; Mass Screening ; Medical diagnosis ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Nucleic Acid Amplification Techniques ; Sensitivity and Specificity ; Telomerase - urine ; Tumors of the urinary system ; Urinary Bladder Neoplasms - diagnosis ; Urinary Bladder Neoplasms - enzymology ; Urinary Bladder Neoplasms - urine ; Urinary system involvement in other diseases. Miscellaneous ; Urinary tract. 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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. DESIGN, SETTING, AND PARTICIPANTS 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. 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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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOME MEASURE 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.</abstract><cop>Chicago, IL</cop><pub>American Medical Association</pub><pmid>16249419</pmid><doi>10.1001/jama.294.16.2052</doi><tpages>5</tpages></addata></record>
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subjects Adult
Aged
Aged, 80 and over
Biological and medical sciences
Biomarkers, Tumor - urine
Bladder cancer
Cancer
Case-Control Studies
Excretory system
General aspects
Humans
Male
Mass Screening
Medical diagnosis
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Nucleic Acid Amplification Techniques
Sensitivity and Specificity
Telomerase - urine
Tumors of the urinary system
Urinary Bladder Neoplasms - diagnosis
Urinary Bladder Neoplasms - enzymology
Urinary Bladder Neoplasms - urine
Urinary system involvement in other diseases. Miscellaneous
Urinary tract. Prostate gland
Urine
Urine - cytology
title Relevance of Urine Telomerase in the Diagnosis of Bladder Cancer
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