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Clinical potential of the ERG oncoprotein in prostate cancer

Nature Reviews Urology volume 9, pages 131–137 (2012)Cite this article

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Abstract

Oncogenic activation of ERG resulting from gene fusion is present in over half of all patients with prostate cancer in Western countries. Although the underlying genetic mechanisms have been extensively studied, evaluation of the ERG oncoprotein—the translational product of ERG gene fusions—has just begun. The robust correlation between ERG oncoprotein detection and gene fusion status enables rapid characterization of this protein in large patient cohorts. Recent studies have focused on characterizing the ERG oncoprotein and determining its potential role in the diagnosis and biological stratification of prostate cancer.

Key Points

  • The highly specific detection of ERG oncoprotein by anti-ERG mAbs offers unprecedented opportunities for the diagnosis of prostate cancer in a large proportion of patients

  • Strong concordance between focally ERG-positive prostatic intraepithelial neoplasia and homogeneously ERG-positive carcinoma suggests a role for ERG in clonal selection of prostate cancer cells during progression from preinvasive to invasive disease

  • Detection of ERG oncoprotein provides an opportunity for stratifying prostate cancers on the basis of a causative oncogenic activation

  • Decreased ERG expression in a subset of advanced tumors may reflect attenuated AR status indicating the dysfunction of androgen signaling

  • Although the prognostic value of ERG gene fusions remains uncertain, careful evaluation of ERG oncoprotein expression levels in combination with other markers may have a potential in prognosing and monitoring disease progression

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Figure 1: Detection of ERG protein expression using the mouse anti-ERG mAb 9FY.
Figure 2: Potential clinical utility of ERG.

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Acknowledgements

Authors express their sincere thanks to Mr Stephen Doyle for assisting with the artwork. The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Army, Department of Defense or the US Government.

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Authors and Affiliations

  1. Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, 1530 East Jefferson Street, Rockville, 20852, MD, USA

    Philip Rosen, Shiv Srivastava & Albert Dobi

  2. Genitourinary Pathology, Joint Pathology Center, 606 Stephen Avenue, Silver Spring, 20910, MD, USA

    Isabell A. Sesterhenn

  3. Walter Reed National Military Medical Center, 4301 Jones Bridge Road, Bethesda, 20814, MD, USA

    Stephen A. Brassell & David G. McLeod

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All authors made substantial contributions to researching data, discussion of content, and writing the manuscript. The Review was then edited by A. Dobi, D. G. McLeod and S. Srivastava before submission.

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Correspondence to Albert Dobi.

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S. Srivastava and A. Dobi declare that they are patent holders/applicants with Biocare Medical. Other authors declare no competing interests.

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Rosen, P., Sesterhenn, I., Brassell, S. et al. Clinical potential of the ERG oncoprotein in prostate cancer. Nat Rev Urol 9, 131–137 (2012). https://doi.org/10.1038/nrurol.2012.10

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