Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (hK2) in serum

Purpose: To investigate the clinical value of measuring human glandular kallikrein 2 (hK2) compared with free and total prostate specific antigen (PSA-F and PSA-T) in serum from patients with prostate disease. Materials and Methods: Serum from healthy controls, from men with benign prostate hyperplasia (BPH), clinically localized prostate cancer (PCa), and advanced PCa were analyzed for hK2 (using an in-house-research assay with detection limit of 0.05 ng./mL and (0.1% cross-reaction with PSA) and for PSA-F and PSA-T (using the Dual Prostatus assay from EG&G Wallac). Results: HK2 concentrations were <0.05 ng./mL in 50/50 healthy volunteers but significantly higher (p <0.0001) and greater than or equal to 0.05 ng./mL in 28/54 (52%) patients with BPH. In comparison to these men, the hK2 levels were significantly higher (p: <0.0001, median 0.085 ng./mL) and greater than or equal to 0.05 ng./mL in 100/136 (74%) men with clinically localized PCa. Compared with localized PCa, the hK2 levels were significantly higher (p <0.0001, median 9.57 ng./mL) and greater than or equal to 0.05 ng./mL in 55/57 (96%) patients with advanced PCa. The median hK2 levels ranged from 1.3 to 1.6% of those of PSA-T in all three patient groups, whereas percent hK2/PSA-F and hK2 x PSA-T/PSA-F levels were significantly higher in cancer patients compared with those with BPH. In the discrimination of clinically localized PCa from EPH, hK2 x PSA-T/PSA-F gave the largest area under the receiver operating curve (AUC = 0.81) and significantly (p = 0.025) larger AUC than PSA-T alone (0.70). Further, at 95% sensitivity there was significant gain in specificity, and at specificity levels of 90 to 95% there was significant gain in sensitivity using the measurements of PSA-T+PSA-F+hK2 compared with analysis of PSA-T and/or percent free PSA. Conclusions: Discrimination of patients with benign prostate disease from those with prostate cancer was significantly enhanced using measurements of hK2 in addition to those of PSA-T and PSB-F. Percent hK2/PSA-F was higher in PCa than in BPH, a phenomena not yet understood.