Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma

Mod Pathol. 2012 Oct;25(10):1378-83. doi: 10.1038/modpathol.2012.97. Epub 2012 Jul 6.

Abstract

ERG gene encodes for an Ets family regulatory transcription factor and is involved in recurrent chromosomal translocations found in a subset of acute myeloid leukemias, prostate carcinomas and Ewing sarcomas. The purpose of this study was to examine the utility of an ERG antibody to detect EWSR1-ERG rearranged Ewing sarcomas. A formalin-fixed paraffin-embedded tissue microarray and whole-tissue sections from 32 genetically characterized Ewing sarcomas were examined: 22 with EWSR1-FLI1, 8 with EWSR1-ERG and 2 with EWSR1-NFATC2. Immunohistochemistry was performed using a rabbit anti-ERG monoclonal antibody directed against the C-terminus of the protein and a mouse anti-FLI1 monoclonal antibody against a FLI1 Ets domain (C-terminus) fusion protein. Immunoreactivity was graded for extent and intensity of positive tumor cell nuclei. ERG labeling was seen in 7/8 EWSR1-ERG cases (predominantly diffuse (5+), moderate to strong), while only 3/24 non-EWR1-ERG cases showed labeling (very weak). FLI1 labeling was observed in 29/31 cases regardless of fusion variant; 23 displayed diffuse (5+) strong/moderate labeling (5/7 EWSR1-ERG, 18/22 EWSR1-FLI1). Both EWSR1-NFATC2 cases had weak reactivity with FLI1 and weak or no reactivity for ERG. In conclusion, strong nuclear ERG immunoreactivity is specific for Ewing sarcomas with EWSR1-ERG rearrangement. In contrast, FLI1 was not specific to rearrangement type, likely because of cross reactivity with the highly homologous Ets DNA-binding domain present in the C-terminus of both ERG and FLI1.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cross Reactions
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry / methods
  • Mice
  • Oncogene Proteins, Fusion / metabolism
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma, Ewing / genetics*
  • Sarcoma, Ewing / metabolism
  • Sarcoma, Ewing / pathology
  • Trans-Activators / genetics*
  • Trans-Activators / immunology
  • Transcription Factors / metabolism
  • Transcriptional Regulator ERG

Substances

  • Antibodies, Monoclonal
  • ERG protein, human
  • EWS-ERG fusion protein, human
  • EWSR1-FLI1 fusion protein, human
  • NFATc2-EWSR1 fusion protein, human
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Regulator ERG