title: Discrimination of prostate cancer from benign disease by plasma measurement of intact, free prostate-specific antigen lacking an internal cleavage site at Lys145-Lys146.
abstract: BACKGROUND
  The proportion of free prostate-specific antigen (PSA) is higher in the sera of patients with benign prostatic hyperplasia compared with patients with prostate cancer (PCa). We developed an immunoassay that measures intact, free PSA forms (fPSA-I), but does not detect free PSA that has been internally cleaved at Lys145-Lys146 (fPSA-N), and investigated whether this form could discriminate patients with PCa from those without PCa.
  
  
  METHODS
  The assay for fPSA-I uses a novel monoclonal antibody (MAb) that does not detect PSA that has been internally cleaved at Lys145-Lys146. A MAb specific for free PSA was used as a capture antibody, and purified recombinant proPSA was used as a calibrator. The concentrations of fPSA-I, free PSA (PSA-F), and total PSA (PSA-T) were analyzed in EDTA-plasma samples (n = 276) from patients who participated in a screening program for PCa (PSA-T, 0.83-76.3 microg/L).
  
  
  RESULTS
  The detection limit of the fPSA-I assay was 0.035 microg/L. Both the measured concentrations of fPSA-I and the concentrations of fPSA-N (calculated as PSA-F - fPSA-I) provided statistically significant discrimination of the two clinical groups. By contrast, PSA-F did not discriminate between these groups. Each of the ratios fPSA-I/PSA-F, fPSA-N/PSA-T, and PSA-F/PSA-T separated cancer samples from noncancer samples in a statistically significant manner (P <0.0001). The ratio fPSA-I/PSA-F was significantly higher in cancer (median, 59%) compared with noncancer samples (47%).
  
  
  CONCLUSIONS
  The ratio fPSA-I/PSA-F is significantly higher in cancer compared with noncancer. The percentages of both fPSA-N/PSA-T and fPSA-I/PSA-F may provide interesting diagnostic enhancements alone or in combination with other markers and require further studies.
authors.affiliation: Department of Biotechnology, University of Turku, Tykistökatu 6A 6th floor, FIN-20520 Turku, Finland. pauliina.nurmikko@utu.fi
authors.forename: P
authors.initials: P
authors.lastname: Nurmikko
authors.forename: K
authors.initials: K
authors.lastname: Pettersson
authors.forename: T
authors.initials: T
authors.lastname: Piironen
authors.forename: J
authors.initials: J
authors.lastname: Hugosson
authors.forename: H
authors.initials: H
authors.lastname: Lilja
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D001798:Blood Proteins / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D015200:Fluoroimmunoassay; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000235:genetics / Q000276:immunology; D011470:Prostatic Hyperplasia / Q000175:diagnosis*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D011994:Recombinant Proteins; D017430:Prostate-Specific Antigen