Detection and isolation of prostate cancer cells from peripheral blood and bone marrow.
OBJECTIVE
To detect and isolate disseminated prostate cancer cells because significant effort has been directed toward defining the characteristics of the primary tumor that predict progression, but little progress has been made on evaluating the disseminated prostate cancer cell. Prostate-specific antigen (PSA) reverse transcriptase-polymerase chain reaction results in the bone marrow (BM) and peripheral blood (PB) of men with prostate cancer suggest many have disseminated cancer cells.


METHODS
Disseminated epithelial cells were isolated from the BM and PB using Miltenyi antibody-coated paramagnetic microparticle technology. In the two-step selection process, anti-CD45 and anti-CD61 were used for negative selection, and anti-human epithelial antigen was used for positive selection. Cells were then stained for Ber-EP4 (a distinct epitope of the human epithelial antigen) and PSA. PSA reverse transcriptase-polymerase chain reaction was performed on an enriched aliquot.


RESULTS
The normal controls were negative. Before prostatectomy, PSA-expressing epithelial cells were detected in 54% of BM and 24% of PB samples. At a median of 4 months after prostatectomy, PSA-expressing cells were detected in 33% of BM and 9% of PB specimens from men without evidence of disease. In men more than 5 years after prostatectomy, PSA-expressing cells were detected in the BM of 4 (29%) of 14, 2 of whom subsequently developed evidence of disease recurrence.


CONCLUSIONS
The findings suggest that dissemination of cells is an early event in prostate cancer that is insufficient for the development of metastases. Isolation will allow interrogation of the phenotype and genotype of the cells.
Ellis
William J
WJ
Department of Urology, University of Washington School of Medicine, Seattle, WA 98105-6510, USA.
Pfitzenmaier
Jesco
J
Colli
Janet
J
Arfman
Edward
E
Lange
Paul H
PH
Vessella
Robert L
RL
D001854:Bone Marrow Cells / Q000473:pathology*; D019046:Bone Marrow Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary; D002469:Cell Separation / Q000379:methods*; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017430:Prostate-Specific Antigen