Molecular Forms of Prostate-specific Antigen and Human Kallikrein 2 as Promising Tools for Early Diagnosis of Prostate Cancer

Molecular Forms of Prostate-specific Antigen and Human Kallikrein 2 as Promising Tools for Early Diagnosis of Prostate Cancer1

Department of Urology [C. S., K. J., M. L., D. S., S. A. L.] and Institute of Laboratory Medicine and Pathological Biochemistry [P. S.], University Hospital Charité, Humboldt University Berlin, D-10098 Berlin, Germany

Abstract

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and for the monitoring of patients with this diagnosis. Molecular forms of PSA and also human kallikrein 2 have been used to discriminate between benign prostatic hyperplasia and prostate cancer as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to α₁-antichymotrypsin (ACT-PSA), and complexed PSA is given together with our results. The ratio of fPSA:tPSA has been shown to improve the specificity of prostate cancer diagnosis on the basis of tPSA measurements. Unnecessary biopsies can be reduced by about 19–64% in the total PSA range of 4–10 μg/liter while only missing 5–10% of cancers. Furthermore, carcinomas in patients with PSA values <4 μg/liter can be detected, indicating an improved sensitivity because of the percent fPSA at low PSA values. ACT-PSA or complexed PSA alone and the calculated derivatives are not superior in their discriminatory power compared with the percent fPSA. The diagnostic significance of the other molecular PSA forms and human kallikrein 2 needs to be evaluated in more extensive clinical trials.

Footnotes

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↵1 Supported by the following sources, fellowships, or grants: Boehringer Ingelheim Foundation (to C. S.), Deutsche Forschungsgemeinschaft (to K. J.), Funds of the German Chemical Industry (to K. J.), Familie-Klee-Stiftung (to M. L.), and the Sonnenfeld-Stiftung (to S. A. L.).
↵2 All authors contributed equally to this report.
↵3 To whom requests for reprints should be addressed, at Department of Urology, University Hospital Charité, Schumannstrasse 20/21, D-10098 Berlin, Germany. Fax: 49-30-28021402; E-mail: klaus.jung{at}charite.de
↵4 The abbreviations used are: PCa, prostate cancer; PSA, prostate-specific antigen; ACT,α ₁-antichymotrypsin; A2M, α₂-macroglobulin; API, α₁-protease-inhibitor; BPH, benign prostatic hyperplasia; bPSA, BPH-nodule-associated PSA; cPSA, complexed form of PSA; DRE, digital rectal examination; fPSA, free, noncomplexed form of PSA; fPSA%, percent free PSA as the ratio of free to total PSA; hK2, human kallikrein 2; PCI, protein C inhibitor; PIN, prostatic intraepithelial neoplasia; ITI, inter-α-trypsin-inhibitor; PI-6, protease inhibitor-6; tPSA, total PSA; ROC, receiver-operating characteristic; proPSA, precursor forms of PSA; thK2, total hK2; prohK2, precursor forms of hK2.
↵5 M. Lein, K. Jung, P. Hammerer, M. Graefen, A. Semjonow, P. Stieber, M. Ossendorf, H-J. Luboldt, B. Brux, C. Stephan, D. Schnorr, and S. A. Loening, unpublished data.
- Accepted August 25, 1900.
- Received April 26, 1900.
- Revision received August 2, 1900.