ERG Transcription Factor as an Immunohistochemical Marker for Vascular Endothelial Tumors and Prostatic Carcinoma

Abstract

ERG, an ETS family transcription factor, is known to be expressed in endothelial cells, and oncogenic ERG gene fusions occur in subsets of prostatic carcinoma, acute myeloid leukemia, and Ewing sarcoma. In this study, we immunohistochemically investigated nuclear ERG expression using a new monoclonal antibody, CPDR ERG-MAb, that is highly specific for detecting ERG protein and ERG-expressing prostate carcinomas. A broad range of vascular endothelial (n = 250), other mesenchymal (n = 973), and epithelial tumors (n = 657) was examined to determine the use of ERG immunohistochemistry in surgical pathology. Only immunostains with ERG-positive normal endothelia (internal control) were considered valid, and only nuclear staining was considered to be positive. In adult tissues, ERG was restricted to endothelial cells and to a subset of bone marrow precursors, but early fetal mesenchyme and subpopulations of fetal cartilage were also positive. In vascular tumors, ERG was expressed in endothelia of all hemangiomas and lymphangiomas, and typically extensively expressed in 96 of 100 angiosarcomas, 42 of 43 epithelioid hemangioendotheliomas, and all 26 Kaposi sarcomas. Among nonvascular mesenchymal tumors, only blastic extramedullary myeloid tumors (7 of 10) and rare Ewing sarcomas (2 of 29) were positive. Among epithelial tumors, 30 of 66 prostatic adenocarcinomas showed focal-to-extensive ERG positivity, with no immunoreactivity in the normal prostate. Other carcinomas and epithelial tumors (n = 643) were ERG negative, with the exception of 1 of 42 large cell undifferentiated pulmonary carcinomas and 1 of 27 mesotheliomas, each of which showed focal nuclear ERG positivity. On the basis of the above observations, ERG is a highly specific new marker for benign and malignant vascular tumors. Among epithelial tumors, ERG shows a great promise as a marker to identify prostatic carcinoma in both primary and metastatic settings.

ERG protein expression and genomic rearrangement status in primary and metastatic prostate cancer—a comparative study of two monoclonal antibodies

“…Of note, angiomatoid and cutaneous fibrous histiocytoma both did not exhibit ERG immunoreactivity. 24 In summary, by demonstrating a broad applicability of both, the rabbit and mouse ERG-MAb, we confirm the feasibilty of ERG IHC in PCa. Given the comfort of performing IHC versus FISH, ERG protein-based stratification of PCa in formalin-fixed paraffinembedded tissue and in decalcified material may evolve into a valuable tool for routine diagnostics.…”

Malignant vascular tumors—an update

“…[23][24][25][26] Given differences in sensitivity and specificity, a panel of antibodies should be used. [23][24][25] Some angiosarcomas co-express epithelial antigens (EMA, Cam5.2 and AE1/3), a fact that should be considered in distinguishing them from carcinoma.…”

Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma

“…Chimeric variants with other Ets family members can exist, and the same tumor can even harbor multiple fusion variants. [9][10][11][12][13] Translocations and deletions of ERG are also seen in some acute myeloid leukemias and ERG overexpression has been associated with poor prognosis. 14,15 In addition, ERG is involved in the development of both hematopoietic and endothelial cells.…”

“…[18][19][20] Several studies have shown anti-ERG antibody useful for prostate carcinoma, metastatic and primary, and prostatic intraepithelial neoplasias. [10][11][12]21,22 The detection of ERG is highly correlated with both ERG rearrangement by fluorescence in-situ hybridization and with ERG mRNA overexpression. 10,12,21 Similar to FLI1, ERG is also found to be expressed in both benign and malignant vascular tumors serving as a helpful marker for endothelial differentiation.…”

“…10,12,21 Similar to FLI1, ERG is also found to be expressed in both benign and malignant vascular tumors serving as a helpful marker for endothelial differentiation. 11,23,24 However, anti-ERG antibody use with Ewing sarcoma has not been previously reported.…”