ERG

(Ets-Related Gene)
Characteristics

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.

Neoplasms

ERG is expresses 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) is directed against the C-terminus of ERG.

Application

For the identification of endothelial differentiation ERG is more sensitive and specific than any other marker. Moreover the interpretation is often easier due to the nuclear reaction. 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. 

Controls

Endothelial cells (internal control).

Selected references

Machado I, Mayordomo-Aranda E, Scotlandi K, Picci P, Llombart-Bosch A. Immunoreactivity using anti-ERG monoclonal antibodies in sarcomas is influenced by clone selection. Pathol Res Pract. 2014 Aug;210(8):508-13. doi:10.1016/j.prp.2014.04.005. PubMed PMID: 24906228.

Miettinen M. Immunohistochemistry of soft tissue tumours - review with emphasis on 10 markers. Histopathology. 2014 Jan;64(1):101-18. doi:10.1111/his.12298. Review. PubMed PMID: 24111893.

Miettinen M, Wang ZF, Paetau A, Tan SH, Dobi A, Srivastava S, Sesterhenn I. ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma. Am J Surg Pathol. 2011 Mar;35(3):432-41. doi: 10.1097/PAS.0b013e318206b67b. PubMed PMID: 21317715.

Stockman DL, Hornick JL, Deavers MT, Lev DC, Lazar AJ, Wang WL. ERG and FLI1 protein expression in epithelioid sarcoma. Mod Pathol. 2014 Apr;27(4):496-501. doi: 10.1038/modpathol.2013.161. PubMed PMID: 24072183.

12.03.17 - MV