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.
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: Melissa Assel; Liisa Sjöblom; Teemu J Murtola; Kirsi Talala; Paula Kujala; Ulf-Håkan Stenman; Kimmo Taari; Anssi Auvinen; Andrew Vickers; Tapio Visakorpi; Teuvo L Tammela; Hans Lilja Journal: Eur Urol Focus Date: 2017-11-11
Authors: Melissa J Assel; Hans David Ulmert; R Jeffery Karnes; Stephen A Boorjian; David W Hillman; Andrew J Vickers; George G Klee; Hans Lilja Journal: Prostate Date: 2019-10-11 Impact factor: 4.104
Authors: Mari T Peltola; Pauliina Niemelä; Kalle Alanen; Martti Nurmi; Hans Lilja; Kim Pettersson Journal: J Immunol Methods Date: 2011-04-28 Impact factor: 2.303
Authors: Sigrid V Carlsson; Mari T Peltola; Daniel Sjoberg; Fritz H Schröder; Jonas Hugosson; Kim Pettersson; Peter T Scardino; Andrew J Vickers; Hans Lilja; Monique J Roobol Journal: BJU Int Date: 2013-02-28 Impact factor: 5.588