Adult Urology Comparative Diagnostic Value of Urine Cytology, UBC-ELISA, and Fluorescence In Situ Hybridization for Detection of Transitional Cell Carcinoma of Urinary Bladder in Routine Clinical Practice Matthias May, Oliver W. Hakenberg, Sven Gunia, Peter Pohling, Christian Helke, Lieselotte Lübbe, Rudolf Nowack, Michael Siegsmund, and Bernd Hoschke OBJECTIVES Fluorescence in situ hybridization (FISH) has been reported to have much better sensitivity for the detection of bladder transitional cell carcinoma (TCC) than urine cytology. We compara- tively tested cytology, FISH, and the cytokeratin-detection test of urinary bladder cancer (UBC) in routine clinical practice. METHODS In a prospective study, FISH, the urinary bladder cancer test (UBC-enzyme-linked immunosor- bent assay [ELISA]), and cytology were used in 166 patients. Of the 166 patients, 62 had primary TCC (group 1), 71 had undergone transurethral resection of primary TCC before routine secondary transurethral resection (group 2), and 33 control had not undergone TCC (group 3). All patients with false-positive test results were followed up for a mean follow-up time of 22 months. RESULTS The overall sensitivity of FISH, UBC-ELISA, and cytology was 53.2% (95% confidence interval 40% to 66%), 40.3% (95% confidence interval 28% to 53%), and 71.0% (95% confidence interval 59% to 83%), respectively (P 0.05). For grade 3 TCC, both FISH and cytology reached a sensitivity of 93.3%. In the 104 patients without TCC, the specificity of FISH, UBC-ELISA, and cytology was 74.0%, 75.0%, and 83.7%, respectively. During follow-up, 33.3% of patients with a false-positive FISH result developed recurrence, as did 23.1% with false- positive UBC results and 29.4% with false-positive cytology findings (P 0.05). Receiver operating characteristic analysis showed an area under the curve for FISH, UBC, and cytology of 0.636, 0.577, and 0.773, respectively. Only cytology and FISH were significantly predictive of a TCC finding on histologic examination (P 0.001 and P = 0.003, respectively). CONCLUSIONS In routine clinical practice, conventional cytology in experienced hands can be superior to FISH. False-positive results with all three test systems used warrant a high suspicion of subclinical precursor lesions of TCC recurrence. UROLOGY 70: 449 – 453, 2007. © 2007 Elsevier Inc. C ystoscopy and urinary cytology are the standard diagnostic tools for the detection and surveil- lance of bladder carcinoma. 1,2 The sensitivity of urinary cytology is limited in well-differentiated transi- tional cell carcinoma (TCC), with an overall median sensitivity of 48% to 61% and median specificity of 94%. 3 Because possibilities for urinary marker-based diagnosis of bladder cancer by developments in molecular biology and proteomics have arisen, the use of urinary cytology in clinical practice is being questioned. A great number of alternative urine markers for the noninvasive detection of bladder cancer have been examined, and some are commercially available for routine use. In meta-analyses, several of these urinary markers have shown greater sen- sitivity than cytology. However, no marker system has yet attained specificity equal to or better than cytology. 3,4 Fluorescence in situ hybridization (FISH) detects chro- mosomal aberrations, and the commercially available test has the potential to detect all genetically unstable blad- der carcinomas. 5,6 Several studies have shown a high sensitivity for the commercial FISH test (UroVysion, Abbott Diagnostics, Germany). 7–13 Another commer- cially available test is the urinary bladder cancer test (UBC-enzyme-linked immunosorbent assay [ELISA], From the Department of Urology, Institute of Pathology, Institute of Clinical Chemistry and Laboratory Diagnostics; Department of Urology, University Hospital, Rostock University, Rostock; and Department of Urology, Vivantes Hospital Am Urban, Berlin, Germany Reprint requests: Matthias May, M.D., Department of Urology, Carl-Thiem Hospital Cottbus, Thiemstrasse 111, Cottbus D-03048, Germany. E-mail: M.May@ctk.de Submitted: August 14, 2006; accepted (with revisions): April 18, 2007 © 2007 Elsevier Inc. 0090-4295/07/$32.00 449 All Rights Reserved doi:10.1016/j.urology.2007.04.023