ERG and FLI1, an Ets Family Transcription Factor and Vascular Marker, Expression in Epithelioid Sarcoma: A Potential Diagnostic Pitfall
David L Stockman, Alexandar J Lazar, Jason L Hornick, Wei-Lien Wang. University of Texas MD Anderson Cancer Center, Houston, TX; Brigham and Women's Hospital, Boston, MA
Background: Epithelioid sarcoma (ES) is a rare, aggressive keratin-positive sarcoma that co-expresses CD34 in 50% of cases and may show cystic degeneration/hemorrhage, mimicking an epithelioid angiosarcoma. Recently, a case of ES was noted to label for ERG, an ETS family regulatory transcription factor that is associated with endothelial differentiation and is a reliable marker for vascular tumors. We investigated the prevalence of nuclear expression of ERG and FLI1, a homologous transcription factor, in ES.
Design: A formalin-fixed paraffin-embedded tissue microarray of 37 ES was examined. Immunohistochemistry was performed following antigen retrieval using a mouse anti-ERG monoclonal antibody to the N-terminus (1:30; 9FY; BioCare Medical), a rabbit anti-ERG monoclonal antibody to the C-terminus (1:2000; EPR3864(2); Epitomics) and a mouse anti-FLI1 monoclonal antibody (1:100; G146-222; BD Biosciences). The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0, no staining; 1+, <5%; 2+, 5% to 25%; 3+, 26% to 50%; 4+, 51% to 75%; and 5+, 76% to 100%), and the intensity of staining was graded as weak, moderate, or strong.
Results: Nuclear staining for the N-terminus of ERG was seen in 19/28 cases: 10 with diffuse (4-5+) strong/moderate labeling; 1 with 2+ moderate labeling and 8 with weak labeling (1-4+, 2 each). Focal staining for the C-terminus of ERG was seen in only 1/29 case (1+ moderate). FLI labeling was seen in nearly all (28/30) cases: 16 with diffuse (5+) predominantly moderate labeling, and 8 cases with diffuse (5+) weak labeling. The remainder had variable moderate (1-3+) or weak (1-4+) FLI1 staining. CD34 was positive in 8/16 cases.
Conclusions: ES can express both ERG and FLI1, which may be a source of diagnostic confusion for a vascular tumor. ERG antibody selection is critical, as those directed against the C-terminus is much more specific for endothelial differentiation than those against the N-terminus. ERG may be of value in the differential diagnosis of epithelioid sarcoma, but should be used in the context of a panel of other antibodies including cytokeratins and INI1.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 13, Monday Afternoon