title: 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: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. wlwang@mdanderson.org
authors: Wei-Lien
authors: WL
authors: Wang
authors: Nimesh R
authors: NR
authors: Patel
authors: Mara
authors: M
authors: Caragea
authors: Pancras C W
authors: PC
authors: Hogendoorn
authors: Dolores
authors: D
authors: López-Terrada
authors: Jason L
authors: JL
authors: Hornick
authors: Alexander J
authors: AJ
authors: Lazar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003429:Cross Reactions; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D000911:Antibodies, Monoclonal; C072312:ERG protein, human; C450460:EWS-ERG fusion protein, human; C576197:EWSR1-FLI1 fusion protein, human; C544391:NFATc2-EWSR1 fusion protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG