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

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.

• Authors: Wei-Lien Wang, Nimesh R Patel, Mara Caragea, Pancras C W Hogendoorn, Dolores López-Terrada, Jason L Hornick, Alexander J Lazar
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 25 Issue 10 Pg. 1378-83 (Oct 2012) ISSN: 1530-0285 [Electronic] United States
• PMID: 22766791 (Publication Type: Journal Article)

Chemical References

• 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

Topics

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