Determination of prostate-specific antigen complexed to alpha 2-macroglobulin in serum increases the specificity of free to total PSA for prostate cancer

Abstract

Objectives. To determine whether prostate-specific antigen (PSA) complexed to alpha 2-macroglobulin (A2M) increases the specificity of free PSA (fPSA) and total PSA (tPSA) for the diagnosis of prostate cancer (PCa). Methods. In a series of 73 patients with PCa and 58 with benign prostatic hyperplasia (BPH), fPSA, tPSA, and PSA complexed with A2M (PSA-A2M) in serum were determined by specific immunoassays. The assay for PSA-A2M was based on the immunoadsorption of immunoreactive PSA in serum and the measurement of the PSA immunoreactivity released by denaturation of PSA-A2M at pH 11.4. Results. The median proportion of PSA-A2M [ % PSA- A2 M= PSA- A2 M/( tPSA+ PSA- A2 M)] and that of fPSA ( % fPSA= fPSA/ tPSA) were significantly lower in patients with PCa (8.2% and 12.4%, respectively) than in patients with BPH (11.6% and 22.5%, P = 0.0014 and P <0.0001, respectively). The median sum of %PSA-A2M and %fPSA was 22.4% in PCa and 38.2% in BPH ( P <0.0001). When the sum of %PSA-A2M and %fPSA was used as a diagnostic test for PCa, 57% of patients with “falsely” elevated PSA concentrations (4 to 10 ng/mL) caused by BPH could be correctly identified without missing patients with PCa compared with 18% of the patients with BPH but not PCa using %fPSA alone. Conclusions. Measurement of the sum of %PSA-A2M and %fPSA in serum significantly improves the cancer specificity of the PSA test compared with the use of tPSA and %fPSA.