title: Diagnosis of bladder cancer by immunocytochemical detection of minichromosome maintenance protein-2 in cells retrieved from urine.
abstract: BACKGROUND
  We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine.
  
  
  METHODS
  Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy.
  
  
  RESULTS
  In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05).
  
  
  CONCLUSIONS
  Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups.
authors.affiliation: Department of Urology, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: K
authors.initials: K
authors.lastname: Saeb-Parsy
authors.forename: A
authors.initials: A
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Scarpini
authors.forename: M
authors.initials: M
authors.lastname: Corcoran
authors.forename: S
authors.initials: S
authors.lastname: Chilcott
authors.forename: M
authors.initials: M
authors.lastname: McKean
authors.forename: B
authors.initials: B
authors.lastname: Thottakam
authors.forename: B
authors.initials: B
authors.lastname: Rai
authors.forename: G
authors.initials: G
authors.lastname: Nabi
authors.forename: D
authors.initials: D
authors.lastname: Rana
authors.forename: M
authors.initials: M
authors.lastname: Perera
authors.forename: K
authors.initials: K
authors.lastname: Stewart
authors.forename: R A
authors.initials: RA
authors.lastname: Laskey
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
authors.forename: N
authors.initials: N
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D018797:Cell Cycle Proteins / Q000652:urine*; D045744:Cell Line, Tumor; D005260:Female; D006417:Hematuria; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000652:urine*; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000652:urine*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2