Electrophoretic Subforms of Free Prostate-Specific Antigen in Serum as Promising Diagnostic Tool in Prostate Cancer Diagnostics

Abstract

To assess the diagnostic performance of the major electrophoretic subforms of free prostate-specific antigen (PSA), named F2 and F3, for differentiating between benign and malignant prostatic disease in men with total PSA (tPSA) concentrations up to 10 microg/L. In sera from 50 patients with prostate cancer (PCa) and 44 men without evidence of malignancy (NPCa), F2 and F3 were quantified by two-dimensional electrophoresis and Western blotting. The F2/F3 ratios were compared with the conventional parameter tPSA and percentage fPSA/tPSA ratio (%fPSA) in univariate and multivariate analyses using receiver operating characteristic analysis. F2 was lower in the NPCa group (median 17%) than in the PCa group (55%), and F3 was greater in the NPCa group (62%) than in the PCa group (45%), resulting in a significantly lower F2/F3 ratio in the NPCa group than in the PCa group (0.32 versus 1.21). The F2/F3 ratio correlated with the %fPSA and prostate volume but not Gleason score, tumor stage, age, or tPSA. The F2/F3 ratio and F2-F3/%fPSA ratio had greater areas under the receiver operating characteristic curves than did tPSA or %fPSA, especially in the subgroup of %fPSA greater than 15%. Models of binary logistic regression confirmed the improvement of diagnostic accuracy using the F2/F3 ratio as an independent variable. Compared with tPSA and %fPSA, the fPSA subforms F2 and F3, assessed as F2/F3 or F2-F3/%fPSA ratios, enhanced the differentiation between men with and without PCa for tPSA levels up to 10 microg/L. Additional characterization of these forms should be performed to develop a feasible assay.