ERG Transcription Factor as a Marker for Vascular Tumors.
Markku Miettinen, Zeng-Feng Wang, Shyh-Han Tan, Albert Dobi, Shiv Srivastava, Isabell Sesterhenn. Armed Forces Institute of Pathology, Washington, DC; Uniformed Services University of Health Sciences, Rockville, MD
Background: Background: ERG transcription factor belongs to the ETS-family of transcription factors and is involved in tumor translocations observed in a subset of prostate carcinomas. Recently, ERG expression has been detected in vascular endothelial cells. In this study we examined ERG-expression in selected normal tissues, vascular tumors, and non-vascular tumors as controls.
Design: A mouse monoclonal antibody to ERG (Clone 9F4) developed at the Center for Prostate Disease Research was used, with a Leica automatic immunostainer using Leica's avidin-biotin free polymer-based detection system. Diaminobenzidine was used the chromogen. Selected normal tissues and 250 vascular and non-vascular tumors were examined for ERG-immunoreactivity. Only tissues that demonstrated endothelial cell nuclear ERG-immunoreactivity were scored, and only nuclear immunoreactivity was counted as positive. Approximately 10% of examined tissues lacked any ERG-immunoreactivity suggesting that this epitope may be sensitive to suboptimal fixation.
Results: In normal skin, breast, tonsil, thymus, liver, kidney, adrenal, pancreas, thyroid, stomach, colon, and term placenta, nuclear ERG-immunoreactivity was restricted to vascular endothelial cells. Nuclear ERG-positivity was consistently observed in endothelial component of benign vascular tumors (n = 6, at minimum in each category): capillary and cavernous hemangiomas of different types, papillary endothelial hyperplasia, and lymphangioma. In spindle cell hemangioma, the endothelial component was positive and spindle cells negative. In malignant vascular tumors, majority of spindle cells and endothelial cells in Kaposi sarcomas (n = 11) and tumor cells in epithelioid hemangioendothelioma (n = 11) and angiosarcoma (n = 17), were positive. All non-vascular tumors (minimum 10 cases of each): glomus tumor, paraganglioma, nodular fasciitis, synovial sarcoma, leiomyosarcoma, gastrointestinal stromal tumor, myxoid liposarcoma, undifferentiated pleomorphic sarcoma (MFH), and malignant mesothelioma were negative showing endothelial cell immunoreactivity only. One pleomorphic liposarcoma showed exceptional nuclear ERG-positivity.
Conclusions: ERG transcription factor is a promising new endothelial cell marker for benign and malignant vascular tumors. Its specificity and sensitivity should be further explored with a larger panel of vascular and non-vascular tumors.
Category: Bone & Soft Tissue
Tuesday, March 1, 2011 2:30 PM
Platform Session: Section E, Tuesday Afternoon