Prostate specific antigen (PSA) is a glycoprotein that is expressed by both normal and neoplastic prostate tissue. PSA is consistently expressed in nearly all prostate cancers, although its level of expression on a per cell basis, especially in very poorly differentiated prostate cancers, is lower than in normal prostate epithelium. The absolute value of serum PSA is useful for determining the extent of prostate cancer and assessing the response to prostate cancer treatment; its use as a screening method to detect prostate cancer is also common, although controversial. (See "Clinical presentation and diagnosis of prostate cancer" and "Screening for prostate cancer".)
The measurement of PSA, causes of abnormal values, and advances in PSA testing will be reviewed here. Recommendations for the clinical use of PSA testing in screening for prostate cancer are presented separately. (See "Screening for prostate cancer".)
PSA EXPRESSION AND PROCESSING
Under normal conditions, PSA is produced as a proenzyme (proPSA) by the secretory cells that line the prostate glands (acini) and secreted into the lumen, where the propeptide is removed to generate active PSA. The active PSA can then undergo proteolysis to generate inactive PSA, of which a small portion then enters the bloodstream and circulates in an unbound state (free PSA). Alternatively, active PSA can diffuse directly into the circulation where it is rapidly bound by protease inhibitors, including alpha-1-antichymotrypsin (ACT) and alpha-2-macroglobulin [1,2].
Although generating less PSA per cell than normal tissue, prostate cancer lacks basal cells, resulting in the disruption of the basement membrane and normal lumen architecture. As a result, the secreted proPSA and several truncated forms have direct access to the circulation resulting in more PSA “leaked” into the blood and a larger fraction of the PSA produced by malignant tissue escapes proteolytic processing (ie, activation of proPSA to active PSA and degradation of active PSA to inactive PSA).
In men with a normal prostate (ie, no cancer and no major inflammation/infection), the majority of free PSA in the serum reflects the mature protein that has been inactivated by internal proteolytic cleavage. In contrast, this cleaved fraction is relatively decreased in prostate cancer. Thus, the percentage of free or unbound PSA is lower in the serum of men with prostate cancer (and conversely, the amount of complexed PSA is higher) compared with those who have a normal prostate or BPH [3-6]. This finding has been exploited in the use of the ratio of free to total PSA and complexed PSA (cPSA) as a means of distinguishing between prostate cancer and BPH as a cause of an elevated PSA. (See 'Serum free and bound PSA' below and 'Complexed PSA' below.)