Key result
High BCL11B and/or GLG1 immunoreactivity in CD99-positive cases demonstrated a specificity of 97.5% and an accuracy of 87.4% for diagnosing Ewing sarcoma.
Why the study?
Ewing sarcoma displays an undifferentiated small-round-cell histomorphology easily confused with differential diagnoses, and the specificity and intra-tumoral expression heterogeneity of potential auxiliary IHC markers BCL11B and GLG1 required validation in a larger independent cohort.
Do BCL11B and GLG1 serve as specific auxiliary IHC markers for diagnosing Ewing sarcoma?
Observational (n=453)
Do BCL11B and GLG1 serve as specific auxiliary IHC markers for diagnosing Ewing sarcoma?
BCL11B and GLG1 are highly specific auxiliary IHC markers that can aid in the diagnosis of Ewing sarcoma, particularly when molecular diagnostics are unavailable.
May aid Ewing sarcoma diagnosis via IHC in CD99+ cases lacking molecular confirmation; leaves open prospective validation before routine adoption.
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.
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Orth et al. (2020) conducted an observational in Ewing sarcoma (n=453). BCL11B and GLG1 immunohistochemistry was evaluated on Specificity and accuracy for diagnosing Ewing sarcoma. High BCL11B and/or GLG1 immunoreactivity in CD99-positive cases demonstrated a specificity of 97.5% and an accuracy of 87.4% for diagnosing Ewing sarcoma.
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