title: DNA cytometric features in biopsies of TaT1 urothelial cell cancer predict recurrence and stage progression more accurately than stage, grade, or treatment modality.
abstract: OBJECTIVE
  To compare retrospectively the predictive value for recurrence and stage progression of DNA ploidy and S-phase fraction by flow cytometry and highly automated ultrafast image cytometry (ICM) in biopsies of TaT1 urothelial cell carcinomas (UCCs) of the urinary bladder with stage, grade, other pathologic features, and treatment.
  
  
  METHODS
  Three experienced pathologists reviewed the stage and grade of 228 UCCs; 193 (85%) consensus cases were analyzed further. We had enough material for single-cell suspensions for both flow cytometry and ICM in 183 cases (94.8%). The 2001 European Society for Analytical Cellular Pathology standards for DNA ICM were followed. The predictive value of DNA features, classic prognosticators (stage, grade, carcinoma in situ, multicentricity), and treatment modality for recurrence and stage progression were analyzed with univariate (Kaplan-Meier) survival and multivariate (Cox model) regression analysis. Ta and T1 cases were analyzed separately.
  
  
  RESULTS
  Of the 228 cases, 88 (51.5%) recurred and 13 (7.6%) progressed. On univariate analysis, most of the DNA features studied were statistically significant. Treatment modality and grade were only prognostic for progression (not for recurrence) and only in Ta cases. On multivariate analysis, DNA ICM features performed best; the strongest recurrence predictor for Ta UCC was a DNA index (DI) of 1.0 versus all others, and for T1 UCC, a DI of less than 1.3 versus 1.3 or greater. The best stage progression predictor for Ta UCCs was a DI of 1.0 plus an S-phase fraction of less than 10%, and for T1 UCCs, a DI of less than 1.3 versus 1.3 or greater. With multivariate analysis, sex, age, grade, carcinoma in situ, multicentricity, and treatment modality were excluded once the DNA ICM features were selected.
  
  
  CONCLUSIONS
  DNA image cytometric features predict recurrence and stage progression in TaT1 UCC biopsies more accurately than classic prognostic factors, independent of treatment modality.
authors.affiliation: Department of Pathology, SIR Hospital, Stavanger, Norway.
authors.forename: Jan P A
authors.initials: JP
authors.lastname: Baak
authors.forename: Marco G W
authors.initials: MG
authors.lastname: Bol
authors.forename: Bianca
authors.initials: B
authors.lastname: van Diermen
authors.forename: E A M
authors.initials: EA
authors.lastname: Janssen
authors.forename: Susanne B K
authors.initials: SB
authors.lastname: Buhr-Wildhagen
authors.forename: Oddvar
authors.initials: O
authors.lastname: Mestad
authors.forename: Per
authors.initials: P
authors.lastname: Øgreid
authors.forename: Kjell-Henning
authors.initials: KH
authors.lastname: Kjellevold
mesh_terms: D000368:Aged; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics*; D009367:Neoplasm Staging / Q000379:methods; D011003:Ploidies; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016196:S Phase / Q000235:genetics; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019459:Urothelium / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm