Proenzyme Forms of Prostate-Specific Antigen in Serum Improve the Detection of Prostate Cancer

Abstract

Introduction: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively]. Methods: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4–10 μg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. Results: The proPSA forms had quantification limits of 0.015–0.025 μg/L in serum, with cross-reactivities 40% proPSA, whereas only 8% of noncancer samples did (P 25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66–0.86), with 90% sensitivity and 36% specificity at 0.04 μg/L. Conclusions: The percentage of proPSA gave better cancer detection in the 4–10 μg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.