ERG and FLI1 protein expression in epithelioid sarcoma

Mod Pathol. 2014 Apr;27(4):496-501. doi: 10.1038/modpathol.2013.161. Epub 2013 Sep 27.


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.

MeSH terms

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antibody Specificity
  • Antigens, CD34 / analysis
  • Biomarkers, Tumor / analysis*
  • Cell Nucleus / chemistry
  • Cell Nucleus / pathology
  • Cross Reactions
  • Humans
  • Immunohistochemistry
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Predictive Value of Tests
  • Proto-Oncogene Protein c-fli-1 / analysis*
  • Proto-Oncogene Protein c-fli-1 / immunology
  • Reproducibility of Results
  • Sarcoma / chemistry*
  • Sarcoma / pathology
  • Tissue Array Analysis
  • Trans-Activators / analysis*
  • Trans-Activators / immunology
  • Transcriptional Regulator ERG


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD34
  • Biomarkers, Tumor
  • ERG protein, human
  • FLI1 protein, human
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Proto-Oncogene Protein c-fli-1
  • Trans-Activators
  • Transcriptional Regulator ERG
  • monoclonal antibody D2-40