Measurement of PSA in Circulation

PSA was first detected in the serum of prostate cancer patients in 1980 [27]. After the clinical study by Stamey et al. serum PSA became a widely used marker for early detection, screening, and monitoring of prostate cancer [2, 9]. However, PSA is not tumor specific but rather organ specific. Thus, prostate cancer, BPH, and prostatitis can all cause increased PSA concentrations in circulation. Manipulation of the prostate, for example, cystoscopy and prostate biopsy, also increase the concentrations of serum PSA [98, 99].

A problem in the clinical use of PSA is that various immunoassays may give different results [100]. Initially this was due to lack of a common standard and differences in the recognition of free PSA and PSA-ACT by the antibodies used [101-103]. This problem has been reduced by the preparation of international standards for free PSA and PSA-ACT [104]. These have made a significant reduction in intermethod variation in proficiency testing programs [104, 105].

4.1. Epitope Mapping

Epitope mapping of 83 monoclonal antibodies to PSA have revealed six partially overlapping antigenic regions on the PSA molecule [106, 107]. One of the six PSA epitopes is completely covered when PSA is complexed with ACT. This epitope contains amino acids 86-91, and constitutes a part of the kallikrein loop of PSA surrounding the active site [108]. Antibodies recognizing this epitope are specific for free, that is, noncomplexed PSA, they inhibit the enzymatic activity of PSA and display no cross-reaction with the structurally similar protein, hK2 [109, 110]. As most antibodies specific for free PSA display no or weak reactivity to reduced PSA on Western blotting, the corresponding epitopes appear to be conformation dependent [110]. The other five epitope-regions are exposed on both free PSA and PSA-ACT, and antibodies binding to these regions react with both forms and are thus called total PSA specific. Some of these antibodies bind with free PSA and PSA-ACT fairly equally, whereas other antibodies bind free PSA preferentially

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