Detection, Isolation and Study of Disseminated Prostate Cancer Cells in the Peripheral Blood and Bone Marrow

Abstract

About 20% to 40% of men who undergo a radical prostatectomy for localized prostate cancer will relapse with progressive disease that frequently results in bone metastases. In addition to numerous studies of the primary tumour, there has been increased attention paid to disseminated cells shed by the tumour and detected in the peripheral blood and bone marrow. It would appear logical that the prostate cancer cells in the blood and the bone marrow that remain following a radical prostatectomy may be more informative in revealing prognostic information than those of the primary tumour which is removed at surgery. The evidence for existence of these disseminated cells in the peripheral blood and bone marrow of prostate cancer patients was first described in the early 1990s using a prostate specific antigen reverse transcriptase polymerase chain reaction (PSA RT-PCR). In general, these studies revealed the presence of disseminated PSA+ epithelial cells (presumed to be prostate cancer cells) early in the disease course and more prevalent in advanced disease than in early disease. Most showed that the bone marrow was more frequently positive than the peripheral blood. As a staging tool, these studies generally showed that PSA RT-PCR was not highly informative since even patients with low stage and early disease frequently showed evidence of disseminated PSA+ cells. Over the past few years, there has been a rapid development of technologies for isolating these disseminated cells for further study. The first step was the enrichment of circulating tumour cells, followed by attempts to isolate and characterize individual cells. The enriched cells have been analysed by a variety of methods, including flow cytometry, immunohistochemistry, and fluorescent in situ hybridisation. Biological characterisation of the cells have included the assessment of telomerase activity, androgen receptor status, and genomic alterations such as loss of heterozygosity and microsatellite instability. Attempts are under way to extend this analysis by utilizing gene expression micro-arrays and array Comparative Genomic Hybridisation (array-CGH). Although these efforts encompass challenges much will be learned about the character of these disseminated cells, including their process of trafficking to distant sites, their potential to seed and grow at these sites and their tendencies for cell dormancy.