Differential diagnosis of prostate cancer and benign prostate hyperplasia using two-dimensional electrophoresis

Abstract

Prostate specific antigen (PSA) is a protease which is characteristic of the prostate. It is widely used as a serum marker for the early diagnosis of prostate cancer (PCa). Nevertheless, for concentrations between 4 and 10 ng/mL, PSA does not enable PCa to be distinguished from benign diseases, such as benign prostate hyperplasia (BPH). In sera, the use of a ratio between free PSA (PSA uncomplexed with protease inhibitor) and total PSA (free PSA and PSA bound to alpha‐1 anti‐chymotrypsin) enables the “gray zone” to be reduced, but an important proportion of patients are still wrongly classed. Using two‐dimensional electrophoresis, we demonstrated using 52 PCa and 40 BPH well‐documented clinical cases that BPH sera show a significantly greater percentage of low‐molecular‐weight free PSA elements (lwPSA) than PCa sera. In our study, the use of a ratio between lwPSA and standard free PSA enables the correct diagnosis of 100% of PCa and 82.5% of BPH cases as against when 73.1% and 42.5% respectively were correctly diagnozed using the total PSA and the free/total PSA ratio. This important finding may be related to differences in the mechanism secreting PSA from the prostate into the bloodstream. We have shown how a tissue marker may be turned into a powerful tumor marker by events probably unrelated to its expression.