Tumor-associated forms of prostate specific antigen improve the discrimination of prostate cancer from benign disease

Abstract

Prostate-specific antigen (PSA) is a widely used serum marker for prostate cancer, but has limited specificity for distinguishing early prostate cancer(PCa) from benign disease since serum PSA can leak from both tumor and prostate tissues with benign disease. Molecular forms of free PSA have been identified that are associated with either benign or malignant prostate tissues. BPSA is a form of free PSA that is associated with benign prostatic hyperplasia(BPH), the predominant benign disease in men. The inactive precursor of PSA, proPSA, is associated with prostate tumors. We have developed research immunoassays with high sensitivity and specificity for BPSA and proPSA. Each of these PSA forms can range from 0-50% of the free PSA in individual serum samples in the total PSA range of 2-10 ng/ml. Typically, BPSA represents from 20-30% of the free PSA in serum, while proPSA ranges from 30-40% of the free PSA. ProPSA greatly improves the early detection of cancer in men with less than 4 ng/ml total PSA. More importantly, proPSA is more highly associated with aggressive cancers than other PSA forms such as PSA-ACT and free PSA. The BPH-associated BPSA and cancer-associated proPSA forms are complementary and provide improved detection of prostate cancer from benign disease.