Fax: +0041-61-265 3194
Early Detection and Diagnosis
Expression patterns of potential therapeutic targets in prostate cancer
Version of Record online: 7 OCT 2004
Copyright © 2004 Wiley-Liss, Inc.
International Journal of Cancer
Volume 113, Issue 4, pages 619–628, 10 February 2005
How to Cite
Zellweger, T., Ninck, C., Bloch, M., Mirlacher, M., Koivisto, P. A., Helin, H. J., Mihatsch, M. J., Gasser, T. C. and Bubendorf, L. (2005), Expression patterns of potential therapeutic targets in prostate cancer. Int. J. Cancer, 113: 619–628. doi: 10.1002/ijc.20615
- Issue online: 30 NOV 2004
- Version of Record online: 7 OCT 2004
- Manuscript Accepted: 3 AUG 2004
- Manuscript Received: 11 APR 2004
- CaP CURE Foundation
- tissue microarray;
Androgen withdrawal is the only effective therapy for patients with advanced prostate cancer, but progression to androgen independence ultimately occurs in almost all patients. Novel therapeutic strategies targeting molecular mechanisms that mediate resistance to hormonal and chemotherapeutic treatment are highly warranted. Here, we aimed to evaluate the expression of potential therapeutic targets in advanced prostate cancer. A tissue microarray (TMA) containing samples from 535 tissue blocks was constructed, including benign prostatic hyperplasia as controls (n = 65), prostatic intraepithelial neoplasia (PIN; n = 78), clinically localized prostate cancers (n = 181), as well as hormone-refractory local recurrences (n = 120) and distant metastases (n = 91). The expression of 13 different proteins was analyzed using immunohistochemistry (Bcl-2, p53, ILK, Syndecan-1, MUC-1, EGFR, HER2/neu, HSP-90, Ep-CAM, MMP-2, CD-10, CD-117 and Ki67). Significant overexpression in hormone-refractory prostate cancer and metastatic tissue compared to localized prostate cancer was found for Ki67 (64% vs. 9%), Bcl-2 (11% vs. 1%), p53 (35% vs. 4%), Syndecan-1 (38% vs. 3%), EGFR (16% vs. 1%) and HER2/neu (16% vs. 0%). Overexpression of CD-117 was restricted to 1 single metastasis. All other markers did not show relevant differences in expression between subgroups. Taken together, p53, Bcl-2, Syndecan-1, EGFR and HER2/neu are preferentially expressed in hormone-refractory and metastatic prostate cancer. Selected inhibition of these targets might offer a strategy to treat advanced tumors and prevent further progression. Treatment decisions should not be based on findings in primary tumors but rather on tissues from recurrent or metastatic lesions.