Five PSA methods compared by assaying samples with defined PSA ratios.

Abstract

Prostate-specific antigen (PSA) has been established as a marker to aid in detection and monitoring of prostate cancer (1)(2). PSA in serum exists predominantly in three forms: free, uncomplexed PSA; PSA covalently complexed to α1-antichymotrypsin (PSA-ACT); and PSA covalently complexed to α2-macroglobulin (PSA-MG) (3). Immunoassays available today recognize free PSA and PSA-ACT but not PSA-MG, and their result for “total PSA” refers to the sum of the free and ACT-bound forms of PSA as measured by the immunoassay. In general, the proportion of free PSA relative to PSA-ACT is lower in prostate cancer patients than in normal subjects or in patients with noncancerous prostatic disease (4). The percentage of free PSA ranges from 5% to 50% when total serum PSA is 4–10 μg/L (5)(6). However, increased serum concentrations of PSA do not necessarily indicate prostate cancer because such values can also occur in cases of benign prostate hyperplasia or prostatitis (7)(8)(9). Assays of total serum PSA differ from one another in an important respect: They do not recognize the free and ACT-bound species of PSA equivalently (10)(11). “Equimolar-response assays” measure equal molar concentrations of free PSA and PSA-ACT equivalently; “skewed-response assays” measure these PSA forms differently (12)(13)(14). The total PSA concentration measured by an equimolar assay depends on only the total concentration of free PSA plus PSA-ACT and is independent of their relative proportions. The interpretation of results reported by skewed-response assays, however, may be misleading because (a) the proportion of free PSA is generally higher in noncancer patients, and (b) the molar response of skewed-response assays …