Benign prostatic hyperplasia-associated prostate-specific antigen (BPSA) shows unique immunoreactivity with anti-PSA monoclonal antibodies

We previously identified a modified molecular form of prostate-specific ant igen that is significantly elevated in the nodular transition zone tissue o f prostates with benign prostatic hyperplasia. This prostate-specific antig en form, designated BPSA, is inactive and contains clipped polypeptide bond s at amino-acid residues Lys145-146 and Lys182-183. BPSA is not elevated in prostate cancer tissues and may therefore be a prostate-specific antigen m arker to better discriminate benign prostatic hyperplasia from early prosta te cancer. In this work we characterize the immunoreactivity of BPSA in com petition assays with prostate-specific antigen using anti-prostate-specific antigen mAb recognizing six different epitopes on the prostate-specific an tigen molecule. One mAb showed > 50% loss of immunoreactivtiy with BPSA com pared with prostate-specific antigen, while the binding of two mAbs was lar gely unaffected and three mAbs had intermediate reactivity. BPSA purified f rom prostate tissue and seminal plasma, as well as BPSA generated in vitro by mild trypsin-treatment were found to have a similar pattern of reactivit y to the six mAbs. However, other forms of inactive seminal plasma prostate -specific antigen, either intact or clipped at Lys145 only, had immunoreact ivity similar to total prostate-specific antigen. These results demonstrate that BPSA has unique immunological properties from other forms of prostate -specific antigen, which should allow the development of BPSA-specific mAbs for the study of benign prostatic hyperplasia. Measurement of BPSA levels in the serum may help discriminate benign prostatic hyperplasia from early prostate cancer.