Abstract
CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity.
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Acknowledgements
Technical support for the experimental trials was provided by the following laboratory assistants: Motoko Tomita, Mami Nakamizo, Juri Godo, Kozue Matsuda, Naomi Tateishi, Hisami Matsumoto, and Noriko Aoki. We also appreciate the technical assistance of the Research Support Center, Kyushu University Graduate School of Medical Sciences.
Case selection and review were accomplished by the following MDs and PhDs: Kiyoshi Saeki, Shinichi Tsuruta, Yuki Kuma, Izumi Kinoshita, Takeshi Iwasaki, Kayoko Nakano, Tatsurou Abe, Naoki Mochidome, Yu Nakaji, Kazuki Takada, Nobuko Yasutake, Yuki Tateishi, Masanobu Sato, Keigo Ozono, Atsushi Abe, Kang-Ring Wang, Risa Hida, Yukihiko Okumura, Tomoko Shinozaki, Kaai Shida, Masaaki Sugimoto, Tetsuyuki Miyazaki, Toshimitsu Nishijima, Hiroshi Koga, Reiko Kumagai, Yukiko Kohno, Yoshiteru Kumagae, Hiroko Imamura, Murasaki Aman, Minako Hirahashi, and Yoshihiro Ohishi.
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This study was approved by the Ethics Committee of Kyushu University (Nos. 25-111, 25-143) and conducted according to the principles embodied in the Declaration of Helsinki. Informed consent was obtained from the subjects or guardians.
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This study was supported by a JSPS KAKEN Grant (No. 25293088) and by funds from the Scholarship Program of the Takeda Science Foundation.
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The authors declare that they have no conflict of interest.
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Yamada, Y., Kuda, M., Kohashi, K. et al. Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes. Virchows Arch 470, 373–380 (2017). https://doi.org/10.1007/s00428-017-2072-8
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DOI: https://doi.org/10.1007/s00428-017-2072-8