Detection of Complexes between Prostate-Specific Antigen and Protease Inhibitors in Plasma

Abstract

Featured Article: Stenman UH, Leinonen J, Alfthan H, Rannikko S, Tuhkanen K, Alfthan O. A complex between prostate-specific antigen and α1-antichymotrypsin is the major form of prostate-specific antigen in serum of patients with prostatic cancer: assay of the complex improves clinical sensitivity for cancer. Cancer Res 1991;51:222–6.2 Prostate-specific antigen (PSA)3 had been in clinical use for several years when we encountered a problem with 2 samples that did not give expected results upon dilution. To explore this finding, we subjected the samples to gel filtration and found that a major part of immunoreactive PSA had a molecular size of about 90 kD rather than the expected size of 30 kD. Because PSA is a protease, we assumed that the 90-kD component was a complex between PSA and a protease inhibitor. We therefore developed assays for possible complexes using a PSA antibody for capture and, as tracer, antibodies to α1-protease inhibitor, α1-antichymotrypsin (ACT), inter-α-trypsin inhibitor, and α2-macroglobulin. PSA complexes with all these inhibitors were detected, but the PSA–ACT complex was by far the most abundant one. At comparable PSA concentrations, that of PSA–ACT was higher in …