Tumor markers: an update on human kallikrein 2.

The development and use of prostate-specific antigen (PSA) in the early detection and staging of prostate cancer has revolutionized management of this disease. The limited specificity of PSA at total PSA (tPSA) levels lower than 10 ng/mL, however, leads to increased numbers of unnecessary prostate biopsies, with attendant patient anxiety, cost, and potential morbidity. Human glandular kallikrein 2 (hK2) is a prostate-specific kallikrein (produced by the prostatic epithelium with approximately 80% DNA sequence homology with PSA) that is emerging as a potential adjunct to PSA as a prostate cancer tumor marker.1 In contrast to PSA, hK2 is a potent protease, with more than 20,000 times the activity of the relatively weak protease PSA. In fact, evidence is increasing that hK2 activates and thus regulates PSA. Some key features of hK2 are summarized in Table 1. Table 1 Key Features of Human Kallikrein 2 (hK2) While PSA production is often decreased in poorly differentiated prostate cancers, hK2 production appears to be increased. This differential production may ultimately be the key to defining the clinical role of hK2. Like PSA, hK2 exists in serum in free (unbound) and complexed (bound) forms. Serum levels of hK2 are much lower than tPSA values in the same patient population, typically ranging from 0% to 10% of PSA levels. These low levels, combined with the molecular similarity of hK2 to PSA, have made reliable assay of hK2 levels relatively difficult. Two groups of investigators have recently tackled the problem of defining the clinical role of hK2 using different techniques, reporting results that raise interest in the potential role of hK2 as a prostate cancer tumor marker.