Immunoreactivity using anti-ERG monoclonal antibodies in sarcomas is influenced by clone selection

The aim of the present study was to explore ERG immunoreactivity in a series of sarcomas, GIST and malignant rhabdoid tumor (MRT), considering the not fully elucidated specificity and sensitivity of this antibody. Paraffin-embedded tissue microarrays from those tumors were stained with anti-ERG against the C-terminus [(EPR3864(2)] and N-terminus (Clone 9FY). EPR3864(2) was positive in almost all angiosarcomas, and MRT. GIST were positive in a large proportion of cases (38.4%), and more than half the synovial sarcomas (52.7%) revealed EPR3864(2) staining. Several chondrosarcomas, osteosarcomas, rhabdomyosarcoma and Ewing's sarcoma family of tumors (ESFT) presented EPR3864(2) expression in a lower number of cases. 9FY was positive in most of the angiosarcomas; however, only sporadic ESFT and synovial sarcoma were positive and the other tumors tested were negative. Fourteen ESFT with EWSR1/Fli-1 gene fusion presented positive nuclear staining for EPR3864(2). Similarly, 5 ESFT with EWSR1/Fli-1 gene fusion presented positive staining for 9FY. We must stress that the difference between the present and previous studies may be due to the source of the anti-ERG employed, anti-ERG against C or N-terminus, protein cross-reactivity and dilution. In conclusion, specificity for ERG staining in sarcomas should be considered with caution and the immunoexpression is undoubtedly influenced by clone and antibody selection.