(Ets-Related Gene)

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. 


Appendix can be recommended as positive and negative tissue control for ERG irrespective of the Ab applied. Virtually all endothelial cells must show a moderate to strong nuclear staining reaction. A weak cytoplasmic staining reaction in endothelial cells with high ERG expression must be accepted, whereas epithelial cells and muscle cells must be negative.
As appendix does not contain any reliable structures with low level ERG expression, supplemental positive tissues / cells may be required. This is needed to identify and monitor an adequately calibrated protocol for the purpose to demonstrate ERG in neoplastic tissues with reduced ERG expression. For this purpose tonsil is very valuable for the rmAb clones EP111 and EPR3894 as these Abs also label lymphocytes. Peripheral T-cells and mantle zone B-cells express a low level staining reaction and it was observed that in the optimal staining results in the prostate specimens, the staining in lymphocytes could be identified even at low magnification (5x). 

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