ERG and FLI1 protein expression in epithelioid sarcoma.
Epithelioid sarcoma is a rare, aggressive keratin-positive sarcoma that co-expresses CD34 in 50% of cases and may mimic an angiosarcoma. Recently, we have observed one case of epithelioid sarcoma that labeled for ERG, an ETS family regulatory transcription factor, which is considered to be a reliable marker for vascular differentiation. We investigated the prevalence of nuclear expression of ERG and FLI1, a homologous transcription factor, in these tumors. A formalin-fixed paraffin-embedded tissue microarray of 37 epithelioid sarcomas was examined. Immunohistochemistry was performed using anti-ERG monoclonal antibody to the N-terminus, anti-ERG monoclonal antibody to the C-terminus and anti-FLI1 monoclonal antibody. Comparison was made with CD34, CD31, and D2-40 labeling. The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0: no staining; 1+: <5%; 2+: 5-25%; 3+: 26-50%; 4+: 51-75%; and 5+: 76-100%), and the intensity of staining was graded as weak, moderate, or strong. Nuclear staining for the N-terminus of ERG was seen in 19 out of 28 cases: 10 with diffuse(4 to 5+) strong/moderate labeling; 1 with 2+ moderate labeling and 8 with weak labeling (1 to 4+, 2 each). Focal staining for the C-terminus of ERG was seen in only 1 out of 29 cases (2+ moderate). FLI1 labeling was seen in nearly all (28 out of 30) cases: 16 with diffuse (5+) predominantly moderate labeling, and 8 cases with diffuse(5+) weak labeling. The remainder had variable moderate (1 to 3+) or weak (1 to 4+) FLI1 staining. CD34 was positive in 22 out of 30 cases and D2-40 was found to be positive in 22 out of 31 cases. All cases were negative for CD31 (0 out of 30). Epithelioid sarcoma can label with antibodies to the N-terminus of ERG, FLI1, and D2-40, which may cause diagnostic confusion for a vascular tumor. A panel of other antibodies including SMARCB1 and CD31 should be used in evaluating these tumors. ERG antibody selection is also critical, as those directed against the C-terminus are less likely to label epithelioid sarcoma.
Departments of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
David L
DL
Stockman
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jason L
JL
Hornick
Departments of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Michael T
MT
Deavers
1] Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA [2] Sarcoma Research Center, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Dina C
DC
Lev
1] Departments of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA [2] Sarcoma Research Center, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Alexander J
AJ
Lazar
Departments of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Wei-Lien
WL
Wang
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000918:Antibody Specificity; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology; D003429:Cross Reactions; D006801:Humans; D007150:Immunohistochemistry; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D011237:Predictive Value of Tests; D051789:Proto-Oncogene Protein c-fli-1 / Q000032:analysis* / Q000276:immunology; D015203:Reproducibility of Results; D012509:Sarcoma / Q000737:chemistry* / Q000473:pathology; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000032:analysis* / Q000276:immunology; D000071230:Transcriptional Regulator ERG
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C072312:ERG protein, human; C078433:FLI1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051789:Proto-Oncogene Protein c-fli-1; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C500987:monoclonal antibody D2-40