ULTRASENSITIVE DETECTION OF PROSTATE-SPECIFIC ANTIGEN BY A TIME-RESOLVED IMMUNOFLUOROMETRIC ASSAY AND THE IMMULITE(R) IMMUNOCHEMILUMINESCENT 3RD-GENERATION ASSAY - POTENTIAL APPLICATIONS IN PROSTATE AND BREASTCANCERS

We report an ultrasensitive time-resolved immunofluorometric assay (TR IFA) for prostate-specific antigen (PSA). The assay is an improvement of our previous report (Clin Chem 1993;39:2108-14) and includes the ut ilization of two monoclonal antibodies and a one-step incubation perio d, which greatly reduces analysis time. The new method demonstrates a superior lower analytical limit of detection (less than or equal to 1 ng/L), a wide dynamic range, absence of a hook effect at 10(6) ng/L PS A, and equimolarity for free PSA and PSA-antichymotrypsin complex. Als o, we have compared several aspects of our TRIFA with a commercially a vailable third-generation assay (Immulite(R)). An evaluation of breast tumor cytosol extracts from 315 patients shows PSA immunoreactivity > 15 ng/g of total protein in 28% and 23% by TRIFA and Immulite analysi s, respectively. Both methods demonstrate a significant association be tween breast tumor PSA immunoreactivity and progesterone and estrogen receptor positivity (P <0.001). Analysis of serum samples obtained for monitoring of postradical prostatectomy patients reveals significant PSA changes at concentrations undetectable by conventional methods, Th e significance of these results as well as the potential applications of ultrasensitive PSA assays in breast and prostate cancers are discus sed.