Identification and Characterization of Viable Bone Metastases from Rapid Autopsies of Androgen Independent Prostate Cancer Patients
R Mehra, Bo Han, C Kumar-Sinha, X Jing, X Cao, J Granger, S Shanker, DC Smith, RB Shah, AM Chinnaiyan, KJ Pienta. University of Michigan, Ann Arbor, MI
Background: Bone is the most common metastatic site for prostate cancer, and osseous metastases are the leading cause of morbidity of this disease. In fact, recent careful autopsy studies prove that 100% of the men who die of prostate cancer have bone involvement. Understanding the biology of prostate cancer and its evolution to an incurable androgen independent phenotype thus warrants an investigation into the genetic and cellular alterations that lead to the seeding and proliferation of these tumor foci in bone, as well as the microenvironment in which these metastases arise.
Design: Between September 1996 to present, 51 rapid autopsies were performed on men who died of advanced androgen independent metastatic prostate cancer at the University of Michigan. As a part of a new protocol, multiple osseous sites including the vertebrae, femurs, and humeri of all patients were longitudinally sectioned and examined for presence of grossly visible metastases. Examination of bone metastases was also guided by the patient's bone scan. Bone marrow tissues harboring either spongy beefy red normal marrow or grossly evident tumor and foci suspicious for tumor were procured for phenotypic assessment and RNA extraction.
Results: We employed a novel technique using gross examination and bone scan guided dissections to procure viable metastatic tumor tissues from involved bones in 13 recent warm autopsies. The presence of viable bone metastasis was confirmed by evaluation of hematoxylin and eosin stained sections of frozen material. The bone metastatic tissues were used for isolating RNA and DNA. Real-time PCR based expression profiling of the most common prostate cancer specific genes, such as PSA, PCA3, ERG, TMPRSS2-ERG, and AMACR was carried out. As expected, PSA and PCA3 show very high levels of expression in all the samples examined, while the expression of AMACR, ERG, and TMPRSS2-ERG showed variable expression across the sample set. Ongoing studies include microarray based comparison of osseous metastatic tissues with non-osseous metastatic tissues within an individual patient as well as in the entire cohort.
Conclusions: Taken together, we describe a versatile and practical approach to describe the phenotypic and molecular/biochemical characteristics of osseous metastasis in men who died of androgen independent prostate cancer.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 131, Monday Morning