Prostate-specific antigen, its molecular forms, and other kallikrein markers for detection of prostate cancer.

P antigen (PSA) is a serine protease produced by the prostate gland at very high concentrations. PSA is secreted into the seminal plasma in high concentrations (0.5 to 5 g/L), where it plays a role in semen liquefaction. The retrograde release of PSA into the bloodstream is a rare event in young, healthy men. It occurs with a frequency of less than one PSA molecule per million secreted PSA molecules, leading to a concentration of less than 4 ng/mL PSA in the serum. The perturbation of the prostate gland architecture often results in excessive escape of PSA into the circulation. Prostate cancer, benign prostatic diseases, and physical trauma to the prostate can result in significant increases in serum PSA. Thus, an elevated serum PSA level is a sensitive marker of prostate gland abnormalities, including prostate cancer and many other conditions affecting the integrity of the prostate gland. These noncancerous alterations have severely challenged the usefulness of PSA as a tumor marker for the early detection of prostate cancer. This disease is the most common malignancy in men, with an estimated 198,100 new cases and 31,500 deaths in 2001.1 Several calculated parameters, such as PSA density, PSA transition zone density, PSA velocity, and age and racespecific PSA ranges, have been only partially successful in enhancing the specificity of PSA and thus reducing somewhat the number of unnecessary prostate biopsies.2 The discovery of different PSA forms, such as free PSA (fPSA) and PSA bound to alpha1-antichymotrypsin (PSA-ACT) in the early 1990s renewed the clinical research on this biomarker.3,4 This review summarizes the current clinical use of fPSA and focuses on new developments regarding the molecular forms of PSA and the promising role of additional kallikreins (especially hK2) for prostate cancer detection.