Prostate-specific antigen (PSA) is a protease that digests the high molecular weight protein of the seminal coagulum into smaller polypeptides. It exists in serum in multiple forms: complexed to alpha-1-anti-chymotrypsin (PSA-ACT complex), unbound (free PSA), and enveloped by alpha-2-macroglobulin. In the early 1990s, the FDA approved the measurement of PSA to diagnose prostate cancer. During the screening, higher total PSA levels observed with a lower percentage of free PSA correlate with higher risks of prostate cancer. Diagnostic assays for NSE are based on the antibody sandwich principle using ELISA or CLIA.