Prostate‑specific antigen (PSA) is a glycoprotein (molecular weight 30000‑34000 daltons) having a close structural relationship to glandular kallikrein. It has the function of a serine protease.
The proteolytic activity of PSA in blood is inhibited by the irreversible formation of complexes with proteinase inhibitors such as alpha‑1‑antichymotrypsin, alpha‑2‑macroglobulin and other acute phase proteins. In addition to being present in these complexes, PSA is also present in blood in the free form, but is proteolytically inactive. PSA tests lack sufficient sensitivity and specificity to be considered ideal or absolutely diagnostic for screening or early detection because PSA is not specific for prostate cancer. PSA is organ specific, being produced primarily by prostatic secretory epithelium, but has long been known to be elevated in non‑malignant conditions such as benign prostatic hyperplasia (BPH). A number of studies have found that the % free PSA was significantly lower in patients having prostate cancer than those with benign disease or normal controls. The ratio fPSA/tPSA has been demonstrated to improve the sensitivity and specificity in patients with tPSA values in the “gray zone” of 4.00‑10.0 ng/mL.
An equimolar tPSA determination is the prerequisite for reliable ratios. In patients receiving therapy, particularly hormone withdrawal therapy, the fPSA/tPSA ratio cannot be utilized to differentiate prostate hyperplasia from cancer of the prostate. Combining tests from different manufacturers to determine tPSA and fPSA can produce erroneous values, since total PSA tests may be standardized by differing methods or detect free PSA to differing degrees.