Gene expression analysis of hormone-refractory prostate cancer in transurethral resection samples

Abstract

4778 Background: After a mean of 15 months, patients with metastatic carcinoma of the prostate (CaP) develop resistance to hormone ablation therapy. However, the underlying molecular mechanisms are still unknown. Our goal is to identify the transcriptional changes that are characteristic for the transition to hormone resistant prostate cancer (HRPC) using oligonucleotide microarrays. A challenge for this approach is the availability of fresh frozen tissue material from patients with HRPC. Here we report the attempt to profile tissue obtained by palliative transurethral resection (TUR). Methods: Indications for palliative TUR were locally progressive tumors with obstruction and voiding problems. HRPC was defined according to the criteria of Scher et al. 1995. Hormone-sensitive CaP tissue has been obtained from patients with incidental CaP during TUR. Samples of benign prostatic hyperplasia (BPH) were collected from age-matched patients undergoing TUR. All tissue samples had been pathologically evaluated and immediately processed (< 10 min) after TUR. Only macrodissected prostate samples with at least 70% tumor content were used for analysis. Results: RNA was successfully isolated from BPH, hormone-sensitive CaP and HRPC samples using a modified purification protocol. The isolated RNA passed well defined quality criteria such as the 28S/18S rRNA ratio (>1,0) and the area under curve (AUC >20%) which were assessed using the Bioanalyzer Nanochip (Agilent Technologies, Palo Alto). Subsequently, RNA integrity was confirmed on human genome FOCUS arrays (Affymetrix Inc., Santa Clara). Conclusions: The reported feasibility of generating expression-profiles from BPH, PCA and HRPC transurethral resection samples now offers the possibility to reveal pathways leading to hormone resistance. Furthermore, the identification of chemopredictive and prognostic marker profiles seems possible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Oncology