title: Immunocyt and the HA-HAase urine tests for the detection of bladder cancer: a side-by-side comparison.
abstract: OBJECTIVE
  The reliable detection of bladder cancer from urine specimen remains an unsolved problem. Especially superficial bladder cancer can be missed with urine tests. We assessed the sensitivity and specificity of the commercial Immunocyt test in a side-by-side comparison with the HA-HAase urine test and cytology. The Immunocyt test measures the immunocytological expression of sulfated mucin-glycoproteins and glycosylated forms of the carcinoembryonic antigen in urine. With the HA-HAase urine test the level of hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are measured in an ELISA-like test.
  
  
  METHODS
  A total of 94 consecutive patients were studied and among these 30 patients had bladder cancer and 64 were controls. Among bladder cancer patients, there were 14 pTa, 9 pT1, 5 pT2 and 2 carcinoma in situ (CIS) transitional cell carcinoma of the bladder, respectively. The controls consisted of 55 patients with a history of bladder cancer but no evidence of tumor at the follow-up cystoscopy and 9 benign prostatic hyperplasia (BPH) patients. The 30 transitional cell cancer specimens had 4 (13%) grade 1 tumors, 15 (50%) grade 2 tumors and 11 (37%) grade 3 tumors. Sensitivity and specificity as well as the positive and negative predictive values of each test were evaluated.
  
  
  RESULTS
  The sensitivity of the HA-HAase urine test (83.3%; 25/30) was significantly higher than the Immunocyt at 63.3% (19/30) (p = 0.038, McNemar test) and cytology (73%; p < 0.05). The specificity of the HA-HAase test (78.1%; 50/64), Immunocyt (75%; 48/64) and cytology (79.7%; 51/64) were comparable. The prevalence of bladder cancer in our study was 31%. The positive predictive value (PPV) of the HA-HAase test (64.1%) was significantly higher than the Immunocyt test (54.3%). The negative predictive value (NPV) of the HA-HAase test (90.9%) was also higher than the Immunocyt test (81.3%). The PPV and NPV values for cytology were 62.9% and 86.4%, respectively. False negative patients in the HA-HAase urine test were 5 pTa tumors (2 G1, 2 G2 and 1 G3). False negative patients in the Immunocyt test were 7 pTa tumors (1 G1 and 6 G2), 3 pT1 (2 G2, 1 G3) and 1 pT2 G3, respectively.
  
  
  CONCLUSIONS
  The sensitivity of the HA-HAase urine test is significantly higher than that of the Immunocyt test to detect bladder cancer. Specificity, as well as the PPV and NPV of the HA-HAase test were higher than that of the Immunocyt test. With a prevalence of 31% bladder cancer patients in all hematuria patients studied, a typical distribution of patients in a urological clinic is presented. Longer follow up of the study patients will give more information on the value of these tests in the detection of bladder cancer.
authors.affiliation: Department of Urology, University Hospital, University of Kiel, Arnold-Heller Str. 7, 24105 Kiel, Germany. stefanhautmann@yahoo.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Hautmann
authors.forename: Marieta
authors.initials: M
authors.lastname: Toma
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Lorenzo Gomez
authors.forename: Martin G
authors.initials: MG
authors.lastname: Friedrich
authors.forename: Torsten
authors.initials: T
authors.lastname: Jaekel
authors.forename: Uwe
authors.initials: U
authors.lastname: Michl
authors.forename: Gretchen L
authors.initials: GL
authors.lastname: Schroeder
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Juenemann
authors.forename: Vinata B
authors.initials: VB
authors.lastname: Lokeshwar
mesh_terms: D014408:Biomarkers, Tumor; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000652:urine; D003581:Cytodiagnosis; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000652:urine; D006821:Hyaluronoglucosaminidase / Q000652:urine; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D011933:Reagent Kits, Diagnostic; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase