MULTIPLE FORMS OF PROSTATE-SPECIFIC ANTIGEN IN SERUM - DIFFERENCES INIMMUNORECOGNITION BY MONOCLONAL AND POLYCLONAL ASSAYS

Prostate-specific antigen (PSA) in serum is primarily complexed with a lpha(1)-antichymotrypsin (alpha(1)-ACT). However, 12-15% of prostate c ancer (PCa) patients present with the predominant form being uncomplex ed (free) PSA (Lilja et al., Clin Chem 1991;37:1618-24). We report tha t commercial immunoassays demonstrate variations in reactivity, especi ally to the uncomplexed form. We fractionated and analyzed commercial controls, PSA complexes prepared in vitro, and sera from patients with PCa or benign prostatic hyperplasia, using molecular sieve chromatogr aphy and Hybritech((R)) Tandem(R)-R, Abbott IMx((R)), and Ciba Coming ACS((TM)) PSA assays. Peak integration of PCa samples demonstrated ACS :Tandem-R ratios of 1-1.3 for PSA/alpha(1)-ACT complex. In contrast, r atios of uncomplexed peaks ranged from 2 to 4, suggesting a greater re activity of the uncomplexed form in the ACS PSA assay. Discrepancies b etween assays, when PSA was measured in unfractionated sera, correlate d directly with the percentage of the uncomplexed form. In controls, f ractionation revealed the presence of uncomplexed PSA only, with ratio s of ACS:Tandem-R and IMx.Tandem-R of 3:1 and 1.8:1, respectively. Imm unoblots of PCa sera detected uncomplexed PSA (similar to 30 kDa) and PSA complexes of similar to 95 kDa (PSA/alpha(1)-ACT) and >200 kDa, in dicative of alpha(2)-macroglobulin. Maximal recognition of all forms o f PSA may be important for early detection of disease progression.