Table of Contents
Definition / general | Essential features | Terminology | Interpretation | Uses by pathologists | Diagrams / tables | Clinical features | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Molecular / cytogenetics images | Board review style question #1 | Board review answer #1Cite this page: Michal M. ERG. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainserg.html. Accessed September 23rd, 2020.
Definition / general
- Transcriptional regulator ERG is a protein encoded by ERG (ETS family transcription factor ERG), which is located at 21q22
- Anti-ERG monoclonal antibodies to the N- or C- terminus are available with a slightly different specificity
- Highly sensitive immunohistochemical marker for vascular differentiation and cartilaginous differentiation (anti-N terminus antibody), expressed also in half of prostatic adenocarcinomas and in Ewing sarcomas with ERG rearrangement
Essential features
- ETS family transcription factor ERG has nuclear staining
- Highly sensitive and quite specific immunohistochemical marker for vascular differentiation, including benign and malignant vascular tumors
- Anti-N terminus ERG monoclonal antibody is a useful marker for certain chondrogenic tumors
- Also expressed in tumors harboring ERG rearrangements: 50% of prostatic adenocarcinomas and 5% of Ewing sarcomas
Terminology
- V-ets erythroblastosis virus E26 oncogene homolog
- ERG3
- p55
- Transcriptional regulator ERG (transforming protein ERG)
Interpretation
- Nuclear staining
Uses by pathologists
- Currently one of the best available markers of endothelial differentiation, including vascular neoplasms such as: hemangioma, hemangioendothelioma, angiosarcoma and Kaposi sarcoma (Am J Surg Pathol 2011;35:432)
- Aids in evaluating lymphovascular invasion
- Anti N terminus ERG monoclonal antibody is a useful marker for certain chondrogenic tumors (J Clin Pathol 2015;68:125, J Clin Pathol 2015;68:1043)
- Differentiating between prostatic small cell carcinoma (positive) and small cell carcinoma of lung or bladder (negative) (Hum Pathol 2011;42:11, Mod Pathol 2011;24:820)
- Nuclear expression can assess the presence of TMPRSS2-ERG or SLC45A3-ERG fusions in prostatic adenocarcinomas; however, since only about 40 - 50% of these tumors harbor ERG rearrangement, and as high grade prostatic intraepithelial neoplasia or other mimics can also be positive, this marker is rarely used for the diagnosis of prostate adenocarcinoma in routine clinical practice, providing useful information (beyond other stains) in only 29% of cases (Am J Surg Pathol 2011;35:1014, Adv Anat Pathol 2018;25:387, Am J Surg Pathol 2014;38:1007)
- Useful marker in distinguishing between leukemia cutis (mainly acute myeloid leukemia) and reactive myeloid infiltrates in the skin (Am J Dermatopathol 2016;38:672)
- Reliably identifies the presence of ERG fusions in Ewing sarcomas (Mod Pathol 2012;25:1378, Genes Chromosomes Cancer 2016;55:340)
- Strong and diffuse nuclear expression is present in EWSR1-SMAD3 rearranged fibroblastic tumor (Am J Surg Pathol 2018;42:1325, Am J Surg Pathol 2018;42:522)
Diagrams / tables
Images hosted on other servers:
ERG rearrangement
Clinical features
- TMPRSS2-ERG fusion may be an early event in prostate cancer, although marked intrafocal heterogeneity exists (Arch Pathol Lab Med 2009;133:1033, Mod Pathol 2013;26:106)
- EWSR1-ERG or FUS-ERG rearrangements are together present in about 5% of Ewing sarcomas (Mod Pathol 2012;25:1378, Genes Chromosomes Cancer 2016;55:340)
- Hematopoietic oncogene that may play a direct role in myeloid leukemia pathogenesis FUS-ERG fusion is present in a subset of acute myeloid leukemias and ERG overexpression in acute myeloid leukemia is associated with poor prognosis (Cancer Res 2009;69:4665, Oncogene 2016;35:1965, J Clin Oncol 2009;27:5031)
Microscopic (histologic) images
Contributed by Michael Michal, M.D., Ph.D.
Epithelioid angiosarcoma
Epithelioid hemangioendothelioma
Epithelioid hemangioma
Metastatic prostate
adenocarcinoma with
TMPRSS2-ERG
fusion
EWSR1-SMAD3 rearranged fibroblastic tumor
Contributed by Brendan C. Dickson, M.D., MSc
Ewing sarcoma
Contributed by Debra Zynger, M.D.
Lymphovascular invasion
Positive staining - normal
- Both blood vessel and lymphatic endothelial cells
- Subpopulation of immature myeloid cells in an adult bone marrow
- Early embryonic subepidermal and paraspinal mesenchyme and periphery of cartilage (Am J Surg Pathol 2011;35:432)
Positive staining - disease
- Highly sensitive and specific marker for benign and malignant vascular tumors (Am J Surg Pathol 2011;35:432)
- Selected chondrogenic tumors (with anti-N terminus ERG monoclonal antibody only)
- EWSR1-SMAD3 rearranged fibroblastic tumors (Am J Surg Pathol 2018;42:1325)
- Weak to moderate expression in most calcifying aponeurotic fibromas (Am J Surg Pathol 2018;42:522)
- Prostatic adenocarcinoma (40 - 60%), high grade prostatic intraepithelial neoplasia (20 - 30%) or benign glands adjacent to prostatic adenocarcinoma and other high grade prostatic intraepithelial neoplasia or benign glands (Am J Surg Pathol 2011;35:1062, Am J Surg Pathol 2011;35:608, Mod Pathol 2011;24:1128)
- Prostatic small cell carcinoma (but not small cell carcinoma from lung or bladder) (Hum Pathol 2011;42:11, Mod Pathol 2011;24:820)
- Nuclear staining for the antibody against N terminus of ERG is present in more than half of epithelioid sarcomas (Am J Surg Pathol 2014;38:1007)
- Ewing sarcomas with EWSR1-ERG or FUS-ERG rearrangement (Mod Pathol 2012;25:1378, Genes Chromosomes Cancer 2016;55:340)
- Subset extramedullary myeloid tumors and acute myeloid leukemias (Am J Dermatopathol 2016;38:672)
Negative staining
- Nuclear expression is absent in the vast majority of nonprostatic carcinomas and other mesenchymal, neuroectodermal and hematopoietic tumors (Am J Surg Pathol 2011;35:432)
Molecular / cytogenetics images
Images hosted on other servers:
Prostatic adenocarcinoma (FISH)
Prostatic small cell carcinoma (FISH)
Board review style question #1
Which of the following neoplasms will most likely be ERG negative?
- Angiosarcoma
- Chondrosarcoma
- Colorectal adenocarcinoma
- Ewing sarcoma with EWSR1-ERG fusion
- Prostate adenocarcinoma with TMPRSS2-ERG fusion
Board review answer #1
