ERG oncoprotein expression in prostate cancer: clonal progression of ERG-positive tumor cells and potential for ERG-based stratification

Prostate Cancer Prostatic Dis. 2010 Sep;13(3):228-37. doi: 10.1038/pcan.2010.23. Epub 2010 Jun 29.

Abstract

Gene fusions prevalent in prostate cancer (CaP) lead to the elevated expression of the ERG proto-oncogene. ERG activation present in 50-70% of prostate tumors underscores one of the most common oncogenic alterations in CaP. Despite numerous reports of gene fusions and mRNA expression, ERG oncoprotein status in CaP still remains to be defined. Furthermore, development of ERG protein-based assays may provide a new dimension to evaluation of gene fusions involving diverse androgen-regulated promoters and the ERG protein-coding sequence. Through exhaustive evaluations of 132 whole-mount prostates (261 tumor foci and over 200 000 benign glands) for the ERG oncoprotein nuclear expression, we demonstrated 99.9% specificity for detecting prostate tumor cells using a highly specific anti-ERG monoclonal antibody. The ERG oncoprotein expression correlated well with fusion transcript or gene fusion in randomly selected specimens. Strong concordance of ERG-positive foci of prostatic intraepithelial neoplasia (PIN) with ERG-positive carcinoma (82 out of 85 sections with PIN, 96.5%) affirms the biological role of ERG in clonal selection of prostate tumors in 65% (86 out of 132) of patients. Conversely, ERG negative PINs were associated with ERG-negative carcinoma. Taken together, the homogeneous and strong ERG expression detected in individual tumors establishes the potential for ERG oncoprotein-based stratification of CaP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism*
  • Adenocarcinoma, Mucinous / pathology
  • Antibodies, Monoclonal*
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • Male
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Prognosis
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / pathology
  • Prostatic Intraepithelial Neoplasia / genetics
  • Prostatic Intraepithelial Neoplasia / metabolism*
  • Prostatic Intraepithelial Neoplasia / pathology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Small Interfering / pharmacology
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Regulator ERG
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • ERG protein, human
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • RNA, Small Interfering
  • Trans-Activators
  • Transcriptional Regulator ERG