title: Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer.
abstract: BACKGROUND
  Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively].
  
  
  METHODS
  Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4-10 microg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity.
  
  
  RESULTS
  The proPSA forms had quantification limits of 0.015-0.025 microg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64-0.74), 0.64 (0.58-0.68), 0.63 (0.58-0.68), and 0.57 (0.51-0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66-0.86), with 90% sensitivity and 36% specificity at 0.04 microg/L.
  
  
  CONCLUSIONS
  The percentage of proPSA gave better cancer detection in the 4-10 microg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.
authors.affiliation: Beckman Coulter, Inc., San Diego, CA, USA. sdmikolajczyk@beckman.com
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Mikolajczyk
authors.forename: William J
authors.initials: WJ
authors.lastname: Catalona
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Evans
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Linton
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Millar
authors.forename: Kathy M
authors.initials: KM
authors.lastname: Marker
authors.forename: Diksha
authors.initials: D
authors.lastname: Katir
authors.forename: Anna
authors.initials: A
authors.lastname: Amirkhan
authors.forename: Harry G
authors.initials: HG
authors.lastname: Rittenhouse
mesh_terms: D000368:Aged; D019540:Area Under Curve; D004792:Enzyme Precursors / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D004792:Enzyme Precursors; D017430:Prostate-Specific Antigen