Eiwitten S100AS en S100A9 samen met de S100 receptor RAGE lijken bepalend voor diagnose beginnende prostaatkanker

10 augustus 2005: Clinical Cancer Research Vol. 11, 5146-5152, July 15, 2005 © 2005 American Association for Cancer Research

De eiwitten S100AS en S100A9 samen met de S100 receptor RAGE, welke een rol spelen in de calcium binding, komen in veel grotere hoeveelheden voor bij mannen met beginnende prostaatkanker dan bij gezonde mannen of bij mannen met goedaardige prostaatafwijkingen blijkt uit Duitse studie. De onderzoekers stellen dat deze manier van diagnosteren wel eens beter zou kunnen zijn of in ieder geval een welkome simpele aanvulling op de PSA meting. Hier het abstract vna deze studie zoals gepresenteerd in Clinical Research van 15 juli 2005.

Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer
Alexander Hermani1, Jochen Hess2, Barbara De Servi1, Senad Medunjanin1, Rainer Grobholz3, Lutz Trojan4, Peter Angel2 and Doris Mayer1
Authors' Affiliations: 1 Research Group Hormones and Signal Transduction and 2 Division of Signal Transduction and Growth Control, German Cancer Research Center, Heidelberg, Germany; and Departments of 3 Pathology, and 4 Urology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany

Requests for reprints: Doris Mayer, Research Group "Hormones and Signal Transduction," Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Phone: 49-6221-423238; Fax: 49-6221-423237; E-mail: d.mayer@dkfz-heidelberg.de

. Purpose: S100 proteins comprise a family of calcium-modulated proteins that have recently been associated with epithelial tumors. We examined the expression of two members of this family, S100A8 and S100A9, together with the S100 receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas and in prostatic intraepithelial neoplasia.

Experimental Design: Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE. In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases. An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH).

Results: S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. There was a high degree of overlap of S100A8 and S100A9 expression patterns and of S100A8 or S100A9 and RAGE, respectively. Frequently, a gradient within the tumor tissue with an increased expression toward the invaded stroma of the prostate was observed. S100A9 serum levels were significantly elevated in cancer patients compared with BPH patients or healthy individuals.

Conclusion: Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.