title: Carbonic anhydrase IX as a diagnostic urinary marker for urothelial bladder cancer.
abstract: Urinary biomarkers are needed to improve the management and reduce the cost of urothelial bladder cancer (UBC); however, none have been recommended yet for clinical practice. This study evaluated carbonic anhydrase IX (CAIX) as a diagnostic urinary biomarker for UBC. CAIX was analyzed by quantitative polymerase chain reaction in urine samples of 196 patients with UBC and 123 controls with hematuria. Paired samples from urine and tumor tissue were evaluated in 16 cases. Data were validated in 155 independent samples. The sensitivity and specificity of CAIX for UBC detection were 86.2% and 95.1%, respectively (area under the curve [AUC]: 90.5%). There was a significant association of CAIX expression between the paired urine and tumor specimens (p=0.002). CAIX showed a significantly higher predictive accuracy than urinary cytology (90.5% vs 71.7%), specifically in low-grade tumors (90.0% vs 61.8%). CAIX expression decreased with increasing tumor stage and grade. Analyses in an independent validation cohort confirmed the high accuracy of CAIX for diagnosing UBC (AUC: 88.3%).
  
  
  RESULTS
  We evaluated carbonic anhydrase IX (CAIX) as a urinary marker for bladder cancer (BCa) using a large series of patients from a single hospital. We found that urinary CAIX has a high sensitivity and specificity for diagnosing BCa.
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Michela
authors.initials: M
authors.lastname: de Martino
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lucca
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Mbeutcha
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Helene G
authors.initials: HG
authors.lastname: Wiener
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Susani
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria. Electronic address: tobias.klatte@meduniwien.ac.at.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000652:urine*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000652:urine*; D016022:Case-Control Studies; D006801:Humans; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D016482:Urinalysis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000652:urine*; D019459:Urothelium / Q000201:enzymology* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Bladder cancer; CA9; Carbonic anhydrase IX; Cystoscopy; Cytology; Diagnosis; Recurrence; Urinary marker