Expression of ERG, an Ets Family Transcription Factor, Specifically Identifies ERG-Rearranged Ewing Sarcoma
Wei-Lien Wang, Nimesh R Patel, Mara Caragea, Dolores Lopez-Terrada, Pancras CW Hogendoorn, Jason L Hornick, Alexander J Lazar. The University of Texas M.D. Anderson Cancer Center, Houston, TX; Texas Children's Hospital/Baylor College of Medicine, Houston, TX; University of Western Ontario, Ontario, Canada; Leiden University Medical Center, Leiden, Netherlands; Brigham and Women's Hospital, Boston, MA
Background: ERG encodes for an Ets family regulatory transcription factor and is involved in recurrent translocations in some acute myeloid leukemias, prostate carcinomas and Ewing sarcomas (ES). The purpose of this study was to examine the utility of an ERG antibody to detect EWSR1-ERG rearranged ES.
Design: Formalin-fixed paraffin-embedded tissue microarray and whole tissue sections of 33 cases of genetically defined ES were examined: 22 with EWSR1-FLI1, 9 with EWSR1-ERG and 2 with EWSR1-NFATC2. Immunohistochemistry was performed using a rabbit anti-ERG monoclonal antibody directed against the C-terminus (1:2000; EPR3864(2); Epitomics) and a mouse anti-FLI1 monoclonal antibody against a FLI1 Ets domain (C-terminus) fusion protein (1:100; G146-222; BD Biosciences). Immunoreactivity was graded for extent and intensity of positive tumor cell nuclei.
Results: ERG labeling was seen in 8/9 EWSR1-ERG cases (predominantly diffuse, moderate to strong), while only 4/24 non-EWR1-ERG cases showed labeling (very weak). FLI1 labeling was observed in 29/32 cases regardless of fusion variant; 23 displayed diffuse strong/moderate labeling (5/8 EWSR1-ERG, 18/21 EWSR1-FLI1). Both EWSR1-NFATC2 cases had weak reactivity with both FLI1 and ERG.
Conclusions: Strong nuclear ERG immunoreactivity is specific for ES with EWSR1-ERG rearrangement. In contrast, FLI1 is not specific to rearrangement type, perhaps due to cross reactivity with the highly homologous Ets DNA binding domain present in both ERG and FLI1. Reagent selection is critical; antibodies against the C-terminus must be employed, as the N-terminus of the ERG or FLI1 protein is substituted by domains of the EWSR1 protein in the active fusion product.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 3, Monday Afternoon