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

Prostate specific antigen (PSA) is a protease which is characteristic of th e 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 r educed, 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 great er percentage of low-molecular-weight free PSA elements (IwPSA) than PCa se ra. In our study, the use of a ratio between IwPSA and standard free PSA en ables the correct diagnosis of 100% of PCa and 82.5% of BPH cases as agains t when 73.1% and 42.5% respectively were correctly diagnozed using the tota l PSA and the free/total PSA ratio. This important finding may be related t o differences in the mechanism secreting PSA from the prostate into the blo odstream. We have shown how a tissue marker may be turned into a powerful t umor marker by events probably unrelated to its expression.