Identification and validation of diagnostic and prognostic markers of prostate cancer

Coordinator:		PD Dr. med Alexander Haese
Institution:		UKE - Klinik für Urologie in Kooperation mit der Martiniklinik
Homepage:		www.martini-klinik.de

The most important parameter for early recognition of prostate cancer (PCa) relies on the determination of the prostate-specific antigen (PSA) serum concentration of the patient. The potential risk of developing prostate cancer raises continuously with increasing PSA serum concentration, even if the tumor is not palpable. A major disadvantage of PSA is its lack of specifity, since PSA is a tissue-specific, but not a cancer-specific marker for the indication of prostate cancer. Suspicious findings based on an elevated PSA value only (between 4-10 ng/ml) occur frequently, since benign tumors can also show an elevated PSA serum concentration. Consequently, physicians are at risk of initiating inappropriate therapy regimens that might cause unnecessary expenses and additional physical and mental stress factors for the patients.

The aim of the present subproject is to develop a routine diagnostic test for the early recognition of prostate cancer based on molecular findings.
The subproject is based on the hypothesis that even tumor-free tissue regions of cancerous prostates may be characterised by a specific gene expression profile, because the tumor cells exert a measurable influence also in tumor-free areas of the organ that is (for instance) mediated by cytokines and growth factors. The existence of such a gene set was confirmed in a preliminary experiment that was performed with a small cohort of patients in cooperation with the German Cancer Research Center in Heidelberg. Optimizing of this gene set is one important task of the project. In a clinical pilot study with 1000 patient samples, the gene set will be further optimized in order to develop a commercial diagnostic test. Along this line RNA is extracted from prostate needle biopsies of healthy patients (no presence of tumor according to routine biopsy) and compared with RNA isolated from tumor-free biopsies of PCa patients. Based on these experiments, a commercial partner (Qiagen GmbH, Hilden, Germany) will manufacture an array-based diagnostic test. In a subsequent prospective study the diagnostic chip is employed for analysis of approximately 2000 patient samples in order to confirm its predictive value for the early recognition of PCa.
This test will be helpful to reduce the number of unnecessary prostate needle biopsies and therefore also the physical and mental stress factors for PCa patients. Furthermore, the test will be instrumental to better identify patients with high-risk PCa early on.




Additional relevant Internet links:
University Medical Center Hamburg-Eppendorf