Abstract 3302: Profiling prostate cancer metastases
Authors: Colm M. Morrissey, Alex Dowell, Martine Roudier, Melanie Ketchandji, Xiaotun Zhang, Shu Chen, Ilsa Colman, Eva Corey, Robert Montgomery, Paul Lange, Beatrice Knudsen, Peter Nelson, Lawrence True, Celestia Higano, Robert Vessella
Journal: Cancer Research (2010)

Abstract Introduction: Prostate cancer (PCa) metastasizes to a number of sites, however, it has a propensity to metastasize to bone. There is considerable variation in sites of metastases, the phenotype of metastases, and bone response in PCa. Our objective was to detail the behavior of PCa metastases in a large cohort of patients who have died of PCa. Methods: Tissue samples used in this study were obtained from seventy patients who had died from advanced PCa and who underwent a rapid autopsy, which was performed under the aegis of the Prostate Cancer Donor Program at the University of Washington. We evaluated the clinical history, sites of metastasis, pathology, biomarker expression and bone response for all 70 patients. We used laser capture microdissection to isolate mRNA from liver, lymph node and bone metastases and performed expression analyses on AgilentTM Oligo Arrays (n=32). Tissue microarrays were used to determine the number of neuroendocrine metastases, androgen receptor positivity, androgen-associated protein expression, and PCa proliferation rates (Ki-67) from 42 patients. Histomorphometry was used to evaluate bone response in ∼20 predetermined bone biopsy sites from 50 of the patients. Results: PCa bone metastases occurred in 90% of our patients that died of PCa. Additionally, the majority of bone metastases were predominantly osteoblastic 71%, with 20% predominantly osteolytic and 9% with a mixed or no bone response. The predominant non-bone sites were lymph nodes, liver, lung and adrenal glands respectively. Seven of 42 patients had metastases with a neuroendocrine phenotype. Nuclear androgen receptor expression was high in bone and low in liver metastases and the correlation between nuclear AR and cytoplasmic PSA was 0.49. Proliferation rates were low in normal prostate increasing in Gleason 3 through 4, and higher in metastases. In a preliminary expression analysis we observed significantly higher expression of CD302, ZNF329, and TMEM79 in the PCa bone metastases compared to soft tissue metastases. Interestingly, bone histomorphometry revealed that the number of TRAcP positive osteoclasts was halved in bone cores from patients treated with bisphosphonates (n=459) compared to bone cores from non-bisphosphonate treated patients (n=284) (p=0.0003). Conclusions: The heterogeneity of PCa metastases both within and between patients is a considerable obstacle in determining the appropriate treatment regime for each individual. Our data highlight these differences, while suggesting patients may be grouped into cohorts with consistent molecular signatures and clinical outcomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3302.