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High specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG positive Ewing sarcoma

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Item Type:Article
Title:High specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG positive Ewing sarcoma
Creators Name:Orth, M.F. and Hölting, T.L.B. and Dallmayer, M. and Wehweck, F.S. and Paul, T. and Musa, J. and Baldauf, M.C. and Surdez, D. and Delattre, O. and Knott, M.M.L. and Romero-Pérez, L. and Kasan, M. and Cidre-Aranaz, F. and Gerke, J.S. and Ohmura, S. and Li, J. and Marchetto, A. and Henssen, A.G. and Özen, Ö. and Sugita, S. and Hasegawa, T. and Kanaseki, T. and Bertram, S. and Dirksen, U. and Hartmann, W. and Kirchner, T. and Grünewald, T.G.P.
Abstract:Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.
Keywords:Ewing Sarcoma, Biomarkers, Immunohistochemistry, Diagnostics, BCL11B, GLG1
Page Range:644
Date:10 March 2020
Official Publication:https://doi.org/10.3390/cancers12030644
PubMed:View item in PubMed

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