Testing New PSA Subforms to Enhance the Accuracy of Predicting Cancer Risk and Disease Outcome in Prostate Cancer

Abstract

Featured Article: Lilja H, Christensson A, Dahlen U, et al. Prostate-Specific Antigen in Serum Occurs Predominantly in Complex with α1-Antichymotrypsin. Clin Chem 1991;37:1618–25.1 Prostate-specific antigen (PSA),2 a kallikrein-like serine protease, is one of the most abundant proteins secreted by the prostate into seminal fluid (1). In the early 1990s, when the study reported in the paper presented here was initiated, serum testing for PSA was coming into widespread use as a means of testing for prostate cancer. Nevertheless, several aspects of PSA in serum remained puzzling; notably, different assays yielded up to 4-fold differences in measured serum PSA concentrations, despite standardization against PSA from seminal fluid. Before our investigation, PSA in seminal fluid was known to occur as active monomeric peptidase (1), but the nature of PSA in blood remained unclear. We speculated that release of catalytic PSA into an abundance of protease inhibitors in blood could prompt PSA to form inhibitor complexes, similar to the way the digestive enzyme trypsin from the pancreas forms enzyme-inhibitor complexes with α1-antitrypsin in blood. A search for interactions between PSA and a panel of common protease inhibitors in serum allowed us …