ERG (Erythroblast transformation-specific [ETS]-related gene) is a proto-oncogene, a member of the ETS family of transcription factors, located on 21q22. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis. The ERG gene encodes for a nuclear protein, also called ERG, which is involved in hematopoietic and endothelial development. ERG remains constitually expressed in endothelial cells in blood and lymphatic vessels, and in bone marrow stem cells.
ERG is expressed in virtually all endothelial neoplasms including haemangioendothelioma, angiosarcoma and Kaposi sarcoma. ERG is overexpressed secondary to gene rearrangement in cases of prostate adenocarcinoma (40-50%, the only type of carcinoma which may express ERG, due to a unique TMPRSS2-ERG gene fusion), gastrointestinal stromal tumour (GIST; 40%*), synovial sarcoma (50%*), meningioma (80%), epithelioid sarcoma (40%), malignant rhabdoid tumour, acute myeloid leukemia and blastic extramedullary myeloid tumor (70%), and rarely Ewing sarcoma / primitive peripheral neuroectodemal tumour (pPNET), chondrosarcoma*, osteosarcoma*, and rhabdomyosarcoma*.
*mostly detected with the Rabbit monoclonal antibody clone EPR3864 (Epitomics) which is directed against the C-terminus of ERG.
For the identification of endothelial differentiation ERG seems more sensitive and specific than any other marker. Moreover, the interpretation is often easier due to the nuclear reaction, which also allows for double stains with cytoplasmic markers like podoplanin. In non-endothelial mesenchymal tumours ERG seems mostly expressed when an antibody against the C-terminus is applied.
Among carcinomas, ERG is highly specific for prostate, while the sensitivity is moderate.
Endothelial cells (internal control).
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