ERG expression in epithelioid sarcoma: a diagnostic pitfall

Abstract

ERG transcription factor is constitutively expressed in endothelial cells. Because benign and malignant vascular endothelia retain the ERG expression, ERG is considered a useful marker for angiosarcomas and related tumors. ERG is also expressed in a subset of prostate carcinomas and Ewing sarcomas due to ERG-involved translocations; therefore, this marker is also of high interest in the study of these malignancies. In this study, we evaluated 109 epithelioid sarcomas for ERG expression, on the basis of an initial observation of an ERG-positive case. We also studied expression of other endothelial antigens in epithelioid sarcoma. ERG was expressed in 38% of epithelioid sarcomas (41/109), usually with a uniform nuclear staining, similar to that seen in angiosarcomas. However, all epithelioid sarcomas were negative for ERG gene rearrangement indicating that ERG expression is not likely related to ERG-involving translocations in epithelioid sarcoma. Other endothelial markers, CD31, claudin 5, and Prox1, were absent in epithelioid sarcomas. The only exception was a pulmonary metastasis of epithelioid sarcoma showing focal CD31 expression, which probably resulted from antigen adsorption onto tumor cell surfaces. However, podoplanin was commonly (7/9) expressed in epithelioid sarcoma; therefore, this marker is not useful in distinguishing epithelioid sarcoma from angiosarcoma. INI1/SMARCB1 gene product was absent in all epithelioid sarcomas (considered here a definitional feature) but was absent from only 1 epithelioid angiosarcoma, indicating its relative specificity for epithelioid sarcoma in this differential diagnostic setting. ERG expression is fairly common in epithelioid sarcoma and should be recognized as a diagnostic pitfall in the differential diagnosis of epithelioid sarcoma and epithelioid angiosarcoma. General lack of endothelial cell-specific markers in epithelioid sarcoma helps in this distinction.

Fig. 1

Epithelioid sarcoma showing a zone of coagulative necrosis. The tumor cells show nuclear positivity for ERG, but lack nuclear INI1-immunoreactivity, in contrast to stromal cells, indicating INI1-loss. CD31 is restricted to vascular endothelial cells.

Fig. 2

Another example of epithelioid sarcoma showing nuclear ERG-positivity, loss of INI1, and lack of CD31 expression.

Fig. 3

Dual-color interphase FISH of ERG-positive epithelioid sarcoma demonstrates presence of an intact ERG locus and lack of the ERG gene rearrangement (no split of red and green fluorescence signals).

Fig. 4

A poorly differentiated epithelioid angiosarcoma shows nuclear positivity for ERG, but exceptionally shows loss of INI1. The tumor cells are strongly positive for CD31.