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Discrimination of Prostate Cancer from Benign Disease by Plasma Measurement of Intact, Free Prostate-specific Antigen Lacking an Internal Cleavage Site at Lys¹⁴⁵-Lys¹⁴⁶

¹ Department of Biotechnology, University of Turku, Tykistökatu 6A 6th floor, FIN-20520 Turku, Finland.
² The Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, Denmark.
³ Department of Urology, Sahlgrenska University Hospital, 5-41345 Göteborg, Sweden.
⁴ Department of Clinical Chemistry, Lund University, University Hospital, S-20502 Malmö, Sweden

^aAuthor for correspondence. Fax 358-2-3338050; e-mail pauliina.nurmikko{at}utu.fi.

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 µg/L).

Results: The detection limit of the fPSA-I assay was 0.035 µg/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.

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