Prostate specific antigen (PSA), a member of the human kallikrein gene family, is a serine protease with chymotrypsin-like activity. The mature form of PSA is a single chain glycoprotein of 237 amino acids containing 7-8% carbohydrate as a single N-linked oligosaccharide side chain. PSA has a molecular weight of approximately 30,000 daltons. The major site of PSA production is the glandular epithelium of the prostate. PSA produced by the prostate is secreted into the seminal fluid in high concentrations. PSA is also present in urine and serum.
The function of PSA is the proteolytic cleavage of gel forming proteins in the seminal fluid resulting in liquefaction of the seminal gel and increased sperm mobility. Low levels of PSA are found in the blood as a result of leakage of PSA from the prostate gland. Increasing levels of PSA are associated with prostatic pathology; including prostatitis, benign prostatic hyperplasia (BPH), and cancer of the prostate. PSA occurs in three major forms in blood. The major immunodetectable form is PSA complexed with the serine protease
inhibitor, alpha-1-antichymotrypsin (PSA-ACT). Uncomplexed, or Free PSA, is the other immunodetectable form of PSA in serum.
The majority of Free PSA'in serum appears to be an inactive form that cannot complex with protease inhibitors and may be either a PSA zymogen or an enzymatically-inactive, cleaved form of PSA. A third form of PSA, a complex with alpha-2-macroglobulin (AMG), is not detectable with current immunoassays for PSA due to the engulfment and subsequent masking of PSA epitopes by the alpha2-macroglobulin molecule.
lmmunoassays have been designed to detect Free PSA, PSA-ACT complex, and Total PSA (immunodetectable forms: e.g., Free PSA and PSA-ACT) .
Using these types of assays, the proportion of Free PSA in the serum was found to be significantly higher
in patients with BPH than in patients with prostate cancer (p < 0.00001) . The proportion, or percent, of Free PSA determined by comparing the concentration of Free PSA to the concentration of Total PSA has been proposed as a way to improve the discrimination between BPH and prostate cancer, especially in those men with intermediate levels of total serum PSA.
Manufacturer’s Reagent package insert Architect Free PSA, August 2017, Abbott Ireland, Diagnostics Division Finisklin Business Park Sligo, Ireland.