What is the Origin of Free PSA?

PSA, a glycoprotein enzyme, was first identified in the 1970s and is primarily produced by the prostate gland. The clinical utility of differentiating between its bound and unbound forms emerged in the 1990s as a refinement of the initial total PSA test, improving its specificity for prostate cancer risk stratification.

What is the Mechanism of Free PSA?

In the presence of prostate cancer, the cellular architecture is often disrupted, leading to increased leakage of PSA into the bloodstream, where a higher proportion of the enzyme is complexed (bound) to serum protease inhibitors. Conversely, in benign conditions like BPH, a greater percentage of the PSA remains in the free, unbound form. Measuring the free-to-total PSA ratio thus provides a functional assessment of the prostate tissue's integrity and pathology.

Free PSA

Meaning

Free PSA is the fraction of Prostate-Specific Antigen (PSA) circulating in the bloodstream that is not bound to serum proteins, such as alpha-1-antichymotrypsin. Total PSA measures both the free and bound forms, but the ratio of free PSA to total PSA is a clinically significant biomarker used to help differentiate between benign prostatic hyperplasia (BPH) and prostate cancer. A lower percentage of free PSA is often associated with a higher probability of prostate malignancy.