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The utility of ETV 1, ETV 4 and ETV 5 RNA in‐situ hybridization in the diagnosis of CIC – DUX sarcomas
Author(s) -
Smith Steven C,
Palanisamy Nallasivam,
Martin Elizabeth,
Almenara Jorge,
McHugh Jonathan B,
Choi EunYoung K,
Lucas David R,
Betz Bryan L,
Thomas Dafydd,
Patel Rajiv M
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13112
Subject(s) - in situ hybridization , fluorescence in situ hybridization , sarcoma , biology , microbiology and biotechnology , rna , chromogenic in situ hybridization , in situ , gene , gene expression , pathology , medicine , chemistry , genetics , chromosome , organic chemistry
Aims A recently characterized group of undifferentiated small round cell sarcomas harbours fusions of the genes CIC and DUX 4 . Studies report a distinctive gene expression profile for these sarcomas, including expression of E26 transformation‐specific ( ETS ) family proto‐oncogenic transcription factors ETV 1, ETV 4 and ETV 5 . To test the utility of an ancillary diagnostic technique for these tumours, we evaluated chromogenic RNA in‐situ hybridization assays for ETV 1 , ETV 4 and ETV 5 as diagnostic adjuncts for this emerging group of highly malignant sarcomas. Methods and results We tested six confirmed CIC – DUX 4 sarcomas and 105 lesions in the differential, including 48 Ewing sarcomas for expression of ETV 1 , ETV 4 and ETV 5 , scoring expression utilizing a previously validated scale. ETV 1 and ETV 4 were positive in five of six cases, while ETV 5 was positive in six of six. No Ewing sarcoma or other sarcoma tested showed coexpression of these transcripts, while one ETV1/ETV4/ETV5 triple positive previously unclassified round cell sarcoma was identified as harbouring a CIC rearrangement by break‐apart fluorescence in‐situ hybridization ( FISH ). Conclusion We identified overexpression of ETV 1 , ETV 4 and ETV 5 transcripts in situ in CIC – DUX 4 sarcomas using a robust assay in routine archival sections. One previously unclassified round cell sarcoma showed ETV 1/4/5 positivity, and was proved to harbour a CIC rearrangement by break‐apart FISH . The sensitivity and specificity observed with our in‐situ hybridization assay implies potential utility as an ancillary diagnostic technique, particularly when faced with limited biopsy samples.

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