Human Cancer Biology Characterization of Bone Metastases from Rapid Autopsies of Prostate Cancer Patients

Purpose: Bone is the most common metastatic site for prostate cancer, and osseous metastases are the leading cause of morbidity from this disease. Recent autopsy studies prove that 100% of men who die of prostate cancer have bone involvement. Understanding the biology of prostate cancer and its evolution to an incurable androgen-independent phenotype requires an understanding of the genetic and cellular alterations that lead to the seeding and proliferation of tumor foci in bone, as well as the microenvironment in which these metastases arise. No intensive studies, however, have been conducted on osseous metastatic tissues from patients with metastatic prostate cancer due to lack of access to such tissues for profiling and other research. Experimental Design: We show, for the first time, a reproducible methodology to obtain high quality clinical tumor tissues metastatic to the bone. This technique allowed the procurement of viable metastatic tumor tissue from involved bones in 13 recent autopsies conducted at the University of Michigan and analyzed the gene expression of these tissues using real-time PCR and microarrays. Results: We present here the discovery of nonossified bone metastases from multiple patients with advanced prostate cancer and their subsequent characterization and comparison to nonosseous metastases from the same patients. Conclusion: This represents a versatile and practical approach that may be employed to characterize the steps inmetastasis and the phenotypic characteristics of osseousmetastasis of prostate cancer and to profile RNA, DNA, and cDNA from tumor samples metastatic to the bone. Clin Cancer Res; 17(12); 3924–32.