Review Article | Published:

Prostate-specific markers to identify rare prostate cancer cells in liquid biopsies

Nature Reviews Urology (2018) | Download Citation

Abstract

Despite improvements in early detection and advances in treatment, patients with prostate cancer continue to die from their disease. Minimal residual disease after primary definitive treatment can lead to relapse and distant metastases, and increasing evidence suggests that circulating tumour cells (CTCs) and bone marrow-derived disseminated tumour cells (BM-DTCs) can offer clinically relevant biological insights into prostate cancer dissemination and metastasis. Using epithelial markers to accurately detect CTCs and BM-DTCs is associated with difficulties, and prostate-specific markers are needed for the detection of these cells using rare cell assays. Putative prostate-specific markers have been identified, and an optimized strategy for staining rare cancer cells from liquid biopsies using these markers is required. The ideal prostate-specific marker will be expressed on every CTC or BM-DTC throughout disease progression (giving high sensitivity) and will not be expressed on non-prostate-cancer cells in the sample (giving high specificity). Some markers might not be specific enough to the prostate to be used as individual markers of prostate cancer cells, whereas others could be truly prostate-specific and would make ideal markers for use in rare cell assays. The goal of future studies is to use sensitive and specific prostate markers to consistently and reliably identify rare cancer cells.

Key points

  • Liquid biopsies, particularly from bone marrow, might enable the detection of recurrent disease before overt lethal metastasis develops.

  • Prostate cancer cells in liquid biopsies, particularly bone marrow, are rare and extremely difficult to identify accurately.

  • Prostate-specific markers analysed using rare cell immunofluorescence assays might help identify rare prostate cancer cells from liquid biopsies.

  • Expression of putative prostate-specific markers is not always constrained to prostate cells. The sensitivity and specificity of assays of expression of candidate markers for rare cells must be ascertained on an individual basis.

  • Immune cells in the blood and bone marrow are a considerable source of nonspecific staining, so measures must be taken to reduce this background staining.

  • Combinatorial staining of multiple prostate-specific markers will increase accuracy for identifying rare prostate cancer cells in liquid biopsies, and improve understanding of the role of important cells in prostate cancer metastasis and aid clinical application.

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Acknowledgements

This work is supported by NCI grants U54CA143803, CA163124, CA093900, and CA143055 as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund and a gift from the Stutt family. E.E.v.d.T. is supported by the Cure for Cancer Foundation. K.C.V. is supported by NCI grant F32CA206394.

Reviewer information

Nature Reviews Urology thanks Y.-J. Lu, A. Strati, and T. Todenhöfer, for their contribution to the peer review of this work.

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Affiliations

  1. Department of Urology, Amsterdam UMC, Amsterdam, Netherlands

    • Emma E. van der Toom
    •  & Theo M. de Reijke
  2. The James Buchanan Brady Urological Institute, Baltimore, MD, USA

    • Haley D. Axelrod
    • , Kenneth J. Pienta
    •  & Kenneth C. Valkenburg
  3. Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Haley D. Axelrod
  4. Department of Urology, Istanbul Medipol University, Istanbul, Turkey

    • Jean J. de la Rosette

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Contributions

E.E.v.d.T., H.D.A., and K.C.V. researched data for the article, E.E.v.d.T., J.J.d.l.R., T.M.d.R., K.J.P., and K.C.V. made substantial contributions to discussions of content. E.E.v.d.T., H.D.A., and K.C.V. wrote the article and all authors reviewed and edited the manuscript before submission.

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The authors declare no competing interests.

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Correspondence to Kenneth C. Valkenburg.

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DOI

https://doi.org/10.1038/s41585-018-0119-5