title: Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of transitional cell carcinoma of the urinary bladder.
abstract: OBJECTIVE
  To assess whether urinary levels of tumor-associated trypsin inhibitor (TATI) would aid in the detection of bladder transitional cell carcinoma (TCC); and to compare diagnostic performance of urinary TATI with that of nuclear matrix protein 22 (NMP22) and barbotage cytology.
  
  
  METHODS
  We determined TATI and NMP22 levels in voided urine from 181 subjects: 153 with previous bladder cancer, 20 with urologic pathology other than bladder cancer, and eight healthy volunteers. TATI was analyzed continuously and categorically on the basis of its quartile distribution. We also measured urinary creatinine and barbotage cytology in 173 and 154 patients, respectively.
  
  
  RESULTS
  Urinary TATI levels were significantly higher in TCC patients with evidence of tumor on cystoscopic evaluation (n = 96) than in control subjects (n = 85; p < 0.001). Higher levels of TATI were associated with positive cytology assay results (p = 0.018), higher NMP22 levels (p < 0.001), and invasive tumor stage (p = 0.026). The area under the receiver operating characteristics (ROC) curve (AUC) of TATI for the detection of TCC was 0.712 (95%CI: 0.637-0.786). The overall AUCs for TATI and NMP22 were not statistically different from each other (p = 0.174). In the >75% sensitivity region of the ROC curves, TATI was consistently more specific than NMP22. TATI, NMP22, and cytology were independently associated with bladder cancer (p = 0.049, p = 0.040, and p < 0.001, respectively). Adjustment of TATI for urinary creatinine levels did not affect any of the outcomes.
  
  
  CONCLUSIONS
  Urinary level of TATI may add independent information to urinary cytology and NMP22 in the detection of bladder TCC. TATI seems to outperform NMP22 for bladder TCC detection.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, 75390-9110, USA. Shahrokh.Shariat@utsouthwestern.edu
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Michael P
authors.initials: MP
authors.lastname: Herman
authors.forename: Roberto
authors.initials: R
authors.lastname: Casella
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D016009:Chi-Square Distribution; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000652:urine; D012372:ROC Curve; D018709:Statistics, Nonparametric; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22; D014359:Trypsin Inhibitor, Kazal Pancreatic; D003404:Creatinine