title: Comparative assessment of urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion with the serum [-2]proprostate-specific antigen-based prostate health index for detection of prostate cancer.
abstract: BACKGROUND
  We compared urinary prostate cancer antigen 3 (PCA3), transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG), and the serum [-2]proprostate-specific antigen ([-2]proPSA)-based prostate health index (Phi) for predicting biopsy outcome.
  
  
  METHODS
  Serum samples and first-catch urine samples were collected after digital rectal examination (DRE) from consented outpatients with PSA 0.5-20 μg/L who were scheduled for prostate biopsy. The PCA3 score (PROGENSA PCA3, Hologic Gen-Probe) and T2:ERG score (Hologic Gen-Probe) were determined. Measurements of serum PSA, free PSA, and [-2]proPSA (Beckman Coulter) were performed, and the percentages of free PSA (%fPSA) and Phi ([-2]proPSA/fPSA × √PSA) were determined.
  
  
  RESULTS
  Of 246 enrolled men, prostate cancer (PCa) was diagnosed in 110 (45%) and there was no evidence of malignancy (NEM) in 136 (55%). A first set of biopsies was performed in 136 (55%) of all men, and 110 (45%) had ≥1 repeat biopsies. PCA3, Phi, and T2:ERG differed significantly between men with PCa and NEM, and these markers showed the largest areas under the ROC curve (AUCs) (0.74, 0.68, and 0.63, respectively). PCA3 had the largest AUC of all parameters, albeit not statistically different from Phi. Phi showed somewhat lower specificities than PCA3 at 90% sensitivity. Combination of both markers enhanced diagnostic power with modest AUC gains of 0.01-0.04. Although PCA3 had the highest AUC in the repeat-biopsy cohort, the highest AUC for Phi was observed in DRE-negative patients with PSA in the 2-10 μg/L range.
  
  
  CONCLUSIONS
  PCA3 and Phi were superior to the other evaluated parameters but their combination gave only moderate enhancements in diagnostic accuracy for PCa at first or repeat prostate biopsy.
authors.affiliation: Department of Urology, Charité-Universitätsmedizin Berlin, Germany. carsten.stephan@charite.de
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Axel
authors.initials: A
authors.lastname: Semjonow
authors.forename: Kai
authors.initials: K
authors.lastname: Schulze-Forster
authors.forename: Henning
authors.initials: H
authors.lastname: Cammann
authors.forename: Xinhai
authors.initials: X
authors.lastname: Hu
authors.forename: Hellmuth-A
authors.initials: HA
authors.lastname: Meyer
authors.forename: Martin
authors.initials: M
authors.lastname: Bögemann
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Frank
authors.initials: F
authors.lastname: Friedersdorff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D012372:ROC Curve
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; C479341:prostate cancer antigen 3, human; D017430:Prostate-Specific Antigen