Does the Phenotyping of Disseminated Prostate Cancer Cells in Blood and Bone Marrow Prior to Radical Prostatectomy Provide Prognostic Information:

摘要

Nearly 20% of men who undergo a radical prostatectomy (RP) later relapse with bone metastases. The cellular events that are predictive of subsequent progressive disease remain unknown. We've focused attention on the detection of disseminated prostate cancer (CaP) cells in the blood and bone marrow. Our hypothesis is that these disseminated cells may provide critical insight regarding biomarkers of use in prognostication. We've developed enrichment and isolation techniques that allow the isolation of individual disseminated CaP cells for study as a pool of cells or single cells. Our proposal was to isolate these cells from 50 patients prior to PP and from 10 patients with advanced disease. Once isolated, the cells are processed and stored for analysis. We greatly exceeded our accrual goal: 131 patients were accrued. We found that 52% of patients prior to radical prostatectomy have disseminated CaP cells in their bone marrow. Molecular and immunohistochemical analyses are revealing the character of these cells. For example, 12% of the specimens show cells with Ki-67 proliferation staining. In addition, 65% of pre- PP specimens show chromosomal aberrations by FISH and aCGH, and RNA expression arrays suggest an enithelial to mesenchymal transition in the disseminated tumor cells.