[23] C-MYC Protein Expression by Immunohistochemistry in CIC-DUX4 Rearranged Sarcomas Is Associated with Trisomy 8

Darya Buehler, Karen Choi, Dafydd G Thomas, Dave R Lucas, Jonathan B McHugh, Alero Inyang, Brian P Rubin, Steven D Billings, John R Goldblum, Rajiv M Patel. Cleveland Clinic, Cleveland, OH; University of Michigan, Ann Arbor, MI

Background: Sarcoma with CIC-DUX4 fusion is a recently described novel subtype of undifferentiated round cell sarcoma of children and young adults. Additional molecular events occurring in these sarcomas are unknown. Two previously published cases reported trisomy 8, and the molecular analysis of one case suggested that an increase in chromosome 8 copy number might drive c-MYC overexpression in these tumors. To further evaluate this potential relationship, we tested six additional cases of CIC-DUX4 sarcomas, including two cases with available karyotype, for c-MYC protein expression by immunohistochemistry.
Design: Six formalin-fixed paraffin embedded cases of EWSR-negative by FISH, CIC-DUX4 rearranged sarcomas were tested for c-MYC expression by immunohistochemistry (rabbit monoclonal Y69, Epitomics, CA, USA). Conventional cytogenetics analysis was performed on two cases. In addition, 5 of 6 cases were stained for ERG as we recently encountered an ERG-immunoreactive CIC-DUX4 tumor which was initially mistaken for a Ewing sarcoma.
Results: The study included 6 patients (5F, 1M, age 20-43), with trunk (2/6) or extremity-based (4/6) tumors. Follow up available in four patients (range 10.2-16.8 mo, mean 13.8 mo) revealed that all four patients developed metastases and died of disease. All six CIC-DUX4 rearranged sarcomas showed moderate to strong diffuse nuclear c-MYC immunoreactivity, including two cases with trisomy 8. ERG also showed strong diffuse nuclear staining in 3 of 5 cases.
Conclusions: Our results further support trisomy 8 as a recurrent chromosomal abnormality in CIC-DUX4 sarcomas and strengthen the evidence that chromosome 8 copy number increase may lead to c-MYC overexpression in these tumors. The strong expression of ERG in a proportion of these tumors may lead to diagnostic confusion but the biologic significance of this finding is not known.
Category: Bone & Soft Tissue

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 12, Tuesday Afternoon


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