Issues on standardization of immunoassays for prostate-specific antigen: a review

The proposed use of serum prostate-specific antigen (PSA) for annual screening of men over age 50 will require careful standardization of the various commercial immunoassays to allow year-to-year comparisons for individual patients. Some current PSA assays give significantly different results on testing the same sample. The standardization process will require several steps. First, a primary antigen standard should be purified from seminal plasma (a convenient source), using a reproducible technique. The modified Sensabaugh-Blake purification of PSA yields a suitable pure antigen. Next, PSA values need to be assigned to PSA-containing serum samples. These secondary serum-based reference materials can be used by manufacturers and regulatory agencies to develop and monitor the performance of PSA assays. In serum, 2 forms of PSA are detected immunologically: a free form (M(r) = 30 kD) and a form complexed with alpha-1-antichymotrypsin (M(r) = 100 kD). Different immunoassays for PSA detect these 2 forms in different molar ratios. The most promising approach to this problem is to select a reference immunoassay that detects both forms of PSA in equal molar ratios. A series of samples containing various and known levels of naturally occurring serum PSA can then serve as secondary serum-based reference materials for calibration of other commercial PSA immunoassays. Equimolar standardization is a useful method for any set of assays that detect free and bound forms of a ligand in differing molar ratios. The technical simplicity and power of this approach should allow early agreement on standardization of PSA immunoassays and will greatly assist PSA screening programs for prostate cancer now in progress.