IN PROSTATISM PATIENTS THE RATIO OF HUMAN GLANDULAR KALLIKREIN TO FREE PSA IMPROVES THE DISCRIMINATION BETWEEN PROSTATE-CANCER AND BENIGN HYPERPLASIA WITHIN THE DIAGNOSTIC GRAY ZONE OF TOTAL PSA 4 TO 10 NG ML/

Objectives. Human glandular kallikrein (hK2) possesses approximately 8 0% structure identity with prostate-specific antigen (PSA). Moreover, messenger ribonucleic acid for hK2 and for PSA is expressed in both be nign and malignant prostatic tissue. We investigated whether the hK2 s erum measurement may improve the detection of prostate cancer (PCa) in patients with total PSA of 4 to 10 ng/mL (diagnostic ''gray zone''). Methods. Blood samples were obtained from 90 consecutive male patients with lower urinary tract symptoms and total PSA values of 4 to 10 ng/ mL. Eighty-one patients underwent transurethral resection of the prost ate and 6 radical prostatectomy. The patients were divided into two gr oups: I, patients with PCa (n = 20) and II, patients with benign prost atic hyperplasia (BPH) (n = 70). An ''in-house'' immunofluorometric as say with analytical sensitivity of 0.01 ng/mL and the functional sensi tivity of 0.05 ng/mL (at this revel the mean coefficient of variation, calculated from the precision profile based on the assays of serum sa mples, was less than 20%) was used to determine serum hK2 concentratio ns. Total PSA, free PSA (ProStatus), and PSA complexed to alpha(1)-ant ichymotrypsin (PSA-ACT) were also measured. Free/total PSA, hK2/total PSA, and hK2/free PSA ratios were calculated. Results. The serum hK2 c ould be detected in all samples and in 76 (84.4%) of 90 samples (PCa, n = 18; BPH, n = 58) at given functional sensitivity level. For these cases the median concentration of hK2 was 0.135 ng/mL in PCa and 0.09 ng/mL in BPH (P < 0.1). The median hK2/total PSA ratio was 2% for PCa and 1.6% for BPH (P < 0.2). The median free/total PSA ratio was 0.122 for PCa and 0.215 for BPH (P < 0.0008) and the hK2/free PSA ratio was 0.139 for PCa and 0.075 for BPH (P < 0.000003). At a 7.2% cutoff, the specificity of hK2/free PSA ratio was 48.2% at 100% sensitivity and in creased to 60.3% at 94.4% sensitivity level (the area under the receiv er operating characteristic curve was 0.86). In comparison, the free/t otal PSA ratio at a 25.2% cutoff had a sensitivity of 94.4% and a spec ificity of 27.6% (area under the curve = 0.76). Conclusions. hK2 was d etected in all sera with total PSA values of 4 to IO ng/mL. Of particu lar clinical interest is the finding that the hK2/free PSA ratio had a better specificity without loss of sensitivity for PCa than total PSA or the PSA free/total ratio within the range of 4 to 10 ng/mL total P SA. hK2 in combination with free PSA may offer a new diagnostic means for PCa detection. UROLOGY 52:360-365, 1998. (C) 1998, Elsevier Scienc e Inc. All rights reserved.