title: Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  Recently, a proteomic study of sera from patients with bladder cancer identified S100A8 and S100A9 as tumor-associated proteins. The present cross-sectional study investigates whether calprotectin, the heterodimer of S100A8/S100A9 may serve as a urinary biomarker for the detection of urothelial bladder cancer.
  
  
  METHODS
  Urinary calprotectin concentrations were assessed in a population of 181 subjects including 46 cases of bladder cancer. 41 cases of renal cell cancer, 54 cases of prostate cancer, and 40 healthy subjects served as control. Acute kidney injury, urinary tract infection, previous BCG-treatment and secondary transurethral resection of the bladder tumor were defined as exclusion criteria. Assessment was performed by enzyme-linked immunosorbent assay and immunohistochemistry detecting calprotectin.
  
  
  RESULTS
  Median calprotectin concentrations (ng/ml) were significantly higher in patients with bladder cancer than in healthy controls (522.3 vs. 51.0, p < 0.001), renal cell cancer (90.4, p < 0.001), and prostate cancer (71.8, p < 0.001). In urothelial carcinoma prominent immunostaining occurred in a subset of tumor cells and in infiltrating myeloid cells. Receiver operating characteristic analysis provided an area under the curve of 0.88 for the differentiation of bladder cancer and healthy control. A cut-off value of 140 ng/ml (determined by Youden's index) resulted in sensitivity and specificity values of 80.4 and 92.5 %. Low grade tumors were associated with significantly lower calprotectin concentrations than high grade tumors (351.9 vs. 1635.2 ng/ml, p = 0.004).
  
  
  CONCLUSIONS
  Urothelial malignancies are associated with highly increased concentrations of calprotecin in the urine. In absence of renal failure and pyuria, calprotectin constitutes a promising biomarker for the detection of bladder cancer.
authors.affiliation: Department of Urology, Charité, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Ebbing
authors.forename: Susanne
authors.initials: S
authors.lastname: Mathia
authors.forename: Felix S
authors.initials: FS
authors.lastname: Seibert
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pagonas
authors.forename: Frederic
authors.initials: F
authors.lastname: Bauer
authors.forename: Barbara
authors.initials: B
authors.lastname: Erber
authors.forename: Karsten
authors.initials: K
authors.lastname: Günzel
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Alexander
authors.initials: A
authors.lastname: Bachmann
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenberger
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Timm H
authors.initials: TH
authors.lastname: Westhoff
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D002277:Carcinoma / Q000175:diagnosis* / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000652:urine; D039841:Leukocyte L1 Antigen Complex / Q000652:urine*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000652:urine; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine; D019459:Urothelium
chemical_list: D014408:Biomarkers, Tumor; D039841:Leukocyte L1 Antigen Complex