Clinical Significance :
PSA is a 340000 dalton monomeric glycoprotein related to the proteses enzyme family. PSA has been found to form stable complexes with two of the major extracellular protease inhibitors in blood, alpha antichymotrypsin (ACT) and alpha macroglobulin (AMG). A small fraction of PSA remains free in blood. In prostate cancer patients PSA complexed with ACT (PSA-ACT) is typically the major form in circulation for about 50% of these patients PSA-ACT accounts for 85% of the total PSA present. Some 12-15% of prostate cancer patients on the other hand present with free (that is, uncomplexed) PSA as the predominant form.
A. Incidence of BPH increases with age:
1. Men aged 60 years : 50%
2. Men aged 80 years : 88%
B. Incidence of symptomatic onset is related to ethhnicity:
1. African American men : onset at age 60 years
2. Caucasian men : onset at age 65 years
Clinical Application:
1. Free PSA is found to comprise significantly (p<0.0001) smaller fraction in patients with untreated prostate cancer than in patients with benign prostatic hypetrophy (BPH).
2. In many men with serum PSA levels less than 10 ng/ml comprising dital PSA levels to free PSA fractions has been proposed as a way to facilitate discrimination between prostate cancer and BPH.
3. The ratio, free PSA/total PSA has been found to be a superior diagnostic indicator than total PSA.
Disadvantage/Limitation
Complex formation with ACT results in exposure of a limited no of antigenic epitopes of PSA, where as complex formation with AMG encapsulates the antigenic epitopes of PSA. Difference in recognition of these multiple forms of PSA by reagent antibodies have contributed to discrepancies between commercial PSA assays