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Basic Research

ERG rearrangement and protein expression in the progression to castration-resistant prostate cancer

Prostate Cancer and Prostatic Diseases volume 17, pages 126–131 (2014)Cite this article

Subjects

Abstract

Background:

Approximately half of the prostate carcinomas are characterized by a chromosomal rearrangement fusing the androgen-regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG. Aim of this study was to comprehensively analyze the role and impact of the ERG rearrangement and protein expression on the progression to castration-resistant (CR) disease.

Methods:

We used a tissue microarray (TMA) constructed from 114 hormone naive (HN) and 117 CR PCs. We analyzed the ERG rearrangement status by fluorescence in situ hybridization and the expression profiles of ERG, androgen receptor (AR) and the proliferation marker Ki67 by immunohistochemistry.

Results:

Nearly half of the PC tissue specimens (HN: 38%, CR: 46%) harbored a TMPRSS2-ERG gene fusion. HN PCs with positive translocation status showed increased tumor cell proliferation (P<0.05). As expected, TMPRSS2-ERG gene fusion was strongly associated with increased ERG protein expression in HN and CR PCs (both P<0.0001). Remarkably, the study revealed a subgroup (26%) of CR PCs with ERG rearrangement but without any detectable ERG protein expression. This subgroup showed significantly lower levels of AR protein expression and androgen-regulated serum PSA (both P<0.05).

Conclusions:

In this study, we identified a subgroup of ERG-rearranged CR PCs without detectable ERG protein expression. Our results suggest that this subgroup could represent CR PCs with a dispensed AR pathway. These tumors might represent a thus far unrecognized subset of patients with AR-independent CR PC who may not benefit from conventional therapy directed against the AR pathway.

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Acknowledgements

This work was supported by the Krebsforschung Schweiz (KFS-02780-02-2011) to CR, by the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG), Emmy-Noether-Program, PE1179/2-1), the Rudolf-Becker-Foundation and the Wilhelm Sander-Foundation (No. 2011.077.1) to SP, by the RO1 DK065977 to SS and by the DoD, CDMRP, PC073614 to SS and AD. We thank Thuy Nguyen and Petra Hirschmann for excellent technical support.

Author information

Authors and Affiliations

  1. Institute for Pathology, University Hospital Basel, University of Basel, Basel, Switzerland

    J R Gsponer, T Vlajnic, L Bubendorf & C Ruiz

  2. Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany

    M Braun & S Perner

  3. Institute of Pathology, Comprehensive Cancer Center, University Hospital Tuebingen, Tuebingen, Germany

    V J Scheble

  4. Division of Urology, St Claraspital, Basel, Switzerland

    T Zellweger

  5. Department of Urology, University Hospital Basel, University of Basel, Basel, Switzerland

    A Bachmann

  6. Department of Anatomy, Physiology, and Genetics, and Institute for Molecular Medicine, Uniformed Services University of the Health Sciences, School of Medicine, Bethesda, MD, USA

    M Srivastava

  7. Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    S-H Tan, A Dobi & S Srivastava

  8. Joint Pathology Center, Silver Spring, MD, USA

    I A Sesterhenn

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  1. J R Gsponer
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  2. M Braun
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Corresponding author

Correspondence to C Ruiz.

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Competing interests

The Henry M. Jackson Foundation for the Advancement of Military Medicine has filed a patent application on the mouse monoclonal anti-ERG antibody, 9FY, on which ST, AD and SS are co-inventors and has been licensed to the Biocare Medical. This study was conducted independent of any involvement from Biocare Medical. The Brigham and Women’s Hospital and the University of Michigan have filed a patent on ETS gene rearrangements in prostate cancer, on which SP is a co-inventor and the diagnostic field of use has been licensed to GenProbe. GenProbe has not played a role in the design and conduct of the study, in the collection, analysis or interpretation of the data and had no involvement in the preparation, review or approval of the manuscript. All the other authors declare no conflict of interest.

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Gsponer, J., Braun, M., Scheble, V. et al. ERG rearrangement and protein expression in the progression to castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 17, 126–131 (2014). https://doi.org/10.1038/pcan.2013.62

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