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Basic Research

ERG protein expression and genomic rearrangement status in primary and metastatic prostate cancer—a comparative study of two monoclonal antibodies

Prostate Cancer and Prostatic Diseases volume 15, pages 165–169 (2012)Cite this article

Subjects

Abstract

Background:

Overexpression of the ERG protein is highly prevalent in prostate cancer (PCa) and commonly results from gene fusions involving the ERG gene. Recently, N-terminal epitope-targeted mouse and a C-terminal epitope-targeted rabbit monoclonal anti-ERG antibody (ERG-MAbs) have been introduced for the detection of the ERG protein. Independent studies reported that immunohistochemistry (IHC) with both ERG-MAbs highly correlates with the underlying ERG gene rearrangement status. However, comparative studies of both antibodies are lacking. Here, we are among the first to compare the mouse ERG-MAb with the rabbit ERG-MAb for their concordance on the same PCa cohort. Furthermore, we assessed whether the ERG protein expression is conserved in lymph node and distant PCa metastases.

Methods:

We evaluated tissue microarrays of 278 specimens containing 265 localized PCa, 29 lymph node, 30 distant metastases and 13 normal prostatic tissues. We correlated ERG protein expression with ERG rearrangement status using an ERG break-apart fluorescence in-situ hybridization assay and IHC of both ERG-MAbs.

Results:

ERG expression and ERG rearrangement status were highly concordant regardless of whether the mouse or rabbit ERG-MAb was used (97.8% versus 98.6%, respectively). Of interest, both ERG antibodies reliably detected the ERG expression in lymph node and distant PCa metastases, of which a subset underwent decalcification. Lymphocytes only revealed immunoreactivity using the rabbit ERG-MAb. If ERG protein expression was present in localized PCa, we observed the same pattern in the corresponding lymph node metastases.

Conclusions:

By demonstrating a broad applicability of IHC to study ERG protein expression using either antibody, this study adds an important step toward a facilitated routine clinical application. Further, we demonstrate that the clonal nature of the ERG rearrangement is not restricted to the genomic level, but proceeds in the proteome. Together, our results simplify future efforts to further eliucidate the biological role of ERG in PCa.

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Acknowledgements

This work was supported by a Grant of the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG), Emmy-Noether-Program, PE1179/2-1) and the Rudolf-Becker-Foundation to S P, and by a Grant of the DFG (WE1104/11-1) and German Cancer Aid (Deutsche Krebshilfe, 107827) to N W The development of mouse ERG-Mab was supported by Grants DoD, CDMRP, Grant PC073614 to A D; and Center for Prostate Disease Research Program.

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Author notes

  1. M Braun and D Goltz: These authors contributed equally to this work

Authors and Affiliations

  1. Institute of Pathology, University Hospital of Bonn, Bonn, Germany

    M Braun, D Goltz, D Adler, W Vogel, D Böhm, G Kristiansen, N Wernert & S Perner

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

    M Braun, W Vogel, D Böhm & S Perner

  3. Division of Hematology and Oncology, Comprehensive Cancer Center, University Hospital of Tuebingen, Tuebingen, Germany

    V Scheble

  4. Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany

    K Sotlar

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

    F Fend

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

    S-H Tan & A Dobi

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  1. M Braun
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Correspondence to S Perner.

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Competing interests

The Brigham and Women's Hospital and the University of Michigan have filed a patent on ETS gene rearrangements in PCa, on which S P is a co-inventor and the diagnostic field of use has been licensed to GenProbe (San Diego, CA, USA). GenProbe did not have 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. The Henry M Jackson Foundation for the Advancement of Military Medicine has filed a patent application on the mouse monoclonal antibody, ERG-MAb, on which S T and A D are co-inventors and has been licensed to the Biocare Medical (Concord, CA, USA). This study was conducted independent of any involvement from Biocare Medical.

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Braun, M., Goltz, D., Adler, D. et al. ERG protein expression and genomic rearrangement status in primary and metastatic prostate cancer—a comparative study of two monoclonal antibodies. Prostate Cancer Prostatic Dis 15, 165–169 (2012). https://doi.org/10.1038/pcan.2011.67

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