A PRECURSOR FORM OF PSA (PPSA) IS A COMPONENT OF THE FREE PSA IN PROSTATE-CANCER SERUM

Objectives, Prostate-specific antigen (PSA) is a widely used serum mar ker for human prostate cancer (PCa). The majority of PSA in serum is p resent as a complex with alpha-1-antichymotrypsin (ACT). In recent yea rs, the ratio of free (uncomplexed) to total PSA has shown improved di scrimination of PCa from benign prostatic hyperplasia. This study exam ines the nature of the free PSA form detected in PCa serum and shows t hat some of the uncomplexed PSA is an inactive precursor of PSA (pPSA) . Methods. Western blot analysis was used to detect clipped, fragment forms of PSA in sera and seminal fluid. Hydrophobic interaction chroma tography-high performance liquid chromatography (HIC-HPLC) was used to identify forms of PSA present in the free PSA population. Pooled sera was passed over a PSA immunoaffinity column, and the eluted PSA compo nents were further resolved by HIC-HPLC. Results. Western blot analysi s of whole sera showed complexed PSA and the intact, approximately 34 kilodalton free PSA. Only negligible levels of clipped or degraded for ms of PSA, as found in seminal fluid, were detected. Column fractions measured for uncomplexed PSA using the Tandem-MP free PSA assay showed that about 25% of the free PSA eluted as pPSA beginning at the [-4]am ino acid. Studies with purified recombinant [-4]pPSA showed that this proenzyme form is inactive and does not complex with ACT. Conclusions. These results suggest that the uncomplexed PSA in PCa serum is primar ily unclipped PSA that contains a significant fraction of pPSA. (C) 19 97, Elsevier Science Inc. All rights reserved.