The detection and isolation of viable prostate-specific antigen positive epithelial cells by enrichment: A comparison to standard prostate-specific antigen reverse transcriptase polymerase chain reaction and its clinical relevance in prostate cancer

Pfitzenmaier, Jesco; Ellis, William J.; Hawley, Sarah; Arfman, Edward W.; Klein, Jeffrey R.; Lange, Paul H.; Vessella, Robert L.

doi:10.1016/j.urolonc.2006.09.018

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 25, Issue 3 , Pages 214-220, May 2007

The detection and isolation of viable prostate-specific antigen positive epithelial cells by enrichment: A comparison to standard prostate-specific antigen reverse transcriptase polymerase chain reaction and its clinical relevance in prostate cancer☆

Jesco Pfitzenmaier, M.D.
- Department of Urology, Medical School, University of Washington, Seattle, WA 98195-6510, USA
- Department of Urology, Medical School, University of Heidelberg, Heidelberg, Germany
William J. Ellis, M.D.
- Department of Urology, Medical School, University of Washington, Seattle, WA 98195-6510, USA
- Corresponding author. Tel.: +1-206-543-3640; fax: +1-206-543-3272.
Sarah Hawley, M.S.
- Public Health Division (Statistics), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Edward W. Arfman, B.A.
- Puget Sound VA Medical Center, Seattle, WA 98108-1597, USA
Jeffrey R. Klein, B.S.
- Department of Urology, Medical School, University of Washington, Seattle, WA 98195-6510, USA
Paul H. Lange, M.D.
- Department of Urology, Medical School, University of Washington, Seattle, WA 98195-6510, USA
Robert L. Vessella, Ph.D.
- Department of Urology, Medical School, University of Washington, Seattle, WA 98195-6510, USA
- Puget Sound VA Medical Center, Seattle, WA 98108-1597, USA

Received 24 January 2006; received in revised form 6 September 2006; accepted 7 September 2006.

Abstract

Purpose

To isolate prostate epithelial cells from the peripheral blood and bone marrow, and compare prostate-specific antigen (PSA) reverse transcriptase polymerase chain reaction (RT-PCR) performed on unenriched or epithelial enriched peripheral blood and bone marrow samples.

Patients and methods

Peripheral blood samples from 371 patients with prostate cancer and 141 controls, and bone marrow samples from 292 patients with prostate cancer and 43 controls were obtained. One aliquot was assessed with PSA RT-PCR. Another was enriched for epithelial cells with paramagnetic immune microbeads and assessed for: (1) PSA immunohistochemistry, (2) PSA RT-PCR, and (3) immunofluorescent detection of epithelial cells.

Results

In the bone marrow (P < 0.01), but not the peripheral blood (P = 0.62), we observed significantly higher detection rates of disseminated PSA expressing epithelial cells after enrichment. The presence of epithelial cells with or without evidence of PSA production was uncommon among controls both in peripheral blood (1% and 0%) and bone marrow (11% and 0%). In patients with active prostate cancer, 46% to 74% had epithelial cells in peripheral blood, and 20% to 64% had PSA expressing epithelial cells. In bone marrow, 55% to 92% had epithelial cells, and 43% to 83% had PSA expressing epithelial cells. Particularly in bone marrow, circulating cells were frequently detected in men without evidence of disease after prostatectomy. With limited follow-up, the detection of epithelial cells or PSA expressing epithelial cells in peripheral blood or bone marrow before radical prostatectomy does not define a population of patients that will have biochemical failure.

Conclusions

Immunomagnetic enrichment frequently detects epithelial, presumably malignant, cells in the peripheral blood and, especially, the bone marrow of patients with prostate cancer. Viable cells can be acquired for gene expression and phenotyping studies.

Keywords: Prostatic neoplasm, Prostate-specific antigen, Reverse transcription-polymerase chain reaction, Recurrence, Metastasis

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☆ This work was supported by the NIDDK O’Brien Center Award, Richard M. Lucas Foundation, Department of Veteran’s Affairs, NIH SPORE Grant, and Deutsche Forschungsgemeinschaft (DFG).