SWI/SNF chromatin remodeling complex status in soft tissue tumors

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26460435
• Research Institution: Kyushu University
• Principal Investigator: 孝橋 賢一 九州大学, 医学研究院, 講師 (10529879)
• Co-Investigator(Kenkyū-buntansha): 山元 英崇 九州大学, 大学病院, 准教授 (30404073)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: SWI/SNF / 尿路上皮癌 / ラブドイド

Outline of Annual Research Achievements

ラブドイド様変化はあらゆる癌腫において見られる現象であり、予後不良因子の一つとしてあげられている。今年度はラブドイド細胞が出現してくるような肉腫様変化をきたす腫瘍として尿路上皮癌を選択し、それを解析した。
1189例の尿路上皮癌を組織学的に再評価し、その中からラブドイド様変化を含む肉腫様変化を抽出したところ10例（0.8％）が該当した。それらについて、SWI/SNF型クロマチンリモデリング因子複合体を構成する蛋白であるSMARCB1 (INI1)、SMARCA4 (BRG1)、SMARCC1 (BAF155)、SMARCA2 (BAF170)、ARID1A蛋白発現を免疫組織化学染色にて評価した。
その結果、10例中5例でいずれかの蛋白が陰性となった。その5例のうち2例はINI1とBRG1両方ともに陰性で、それに加えてBAF155ないしBAF170も陰性であった。それ以外の3例では各々1種類ずつの蛋白（BRG1が2例、BAF170が1例）が陰性であった。
軟部腫瘍では、上記構成因子の中でもINI1遺伝子異常が悪性ラブドイド腫瘍や類上皮肉腫に認められるが、INI1蛋白陽性の場合には、それ以外の蛋白発現異常が報告されている。肉腫のみならず、上皮性腫瘍における、ラブドイド様変化においても同様のことが今回の結果で明らかになった。これらのことはあらゆる癌腫においてみることができる形態学的に特徴のあるラブドイド様変化は、クロマチンリモデリング因子複合体を構成する蛋白異常に起因する可能性が考えられた。

Research Products

• [Journal Article] Primary extraskeletal osteosarcoma: a clinicopathological study of 18 cases focusing on MDM2 amplification status. (2017)
  • Author(s): Yamashita K, Kohashi K, Yamada Y, Nishida Y, Urakawa H, Oda Y, Toyokuni S.
  • Journal Title: Hum Pathol. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1016/j.humpath.2017.02.007.
  • Peer Reviewed
• [Journal Article] Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes. (2017)
  • Author(s): Yamada Y, Kuda M, Kohashi K, Yamamoto H, Takemoto J, Ishii T, Iura K, Maekawa A, Bekki H, Ito T, Otsuka H, Kuroda M, Honda Y, Sumiyoshi S, Inoue T, Kinoshita N, Nishida A, Yamashita K, Ito I, Komune S, Taguchi T, Iwamoto Y, Oda Y.
  • Journal Title: Virchows Arch. Volume: 470 Pages: 373-380
  • DOI: 10.1007/s00428-017-2072-8.
  • Peer Reviewed
• [Journal Article] Oncogenic roles of SMARCB1/INI1 and its deficient tumors. (2017)
  • Author(s): Kohashi K, Oda Y.
  • Journal Title: Cancer Sci. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1111/cas.13173.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. (2017)
  • Author(s): Iura K, Maekawa A, Kohashi K, Ishii T, Bekki H, Otsuka H, Yamada Y, Yamamoto H, Harimaya K, Iwamoto Y, Oda Y.
  • Journal Title: Hum Pathol. Volume: 61 Pages: 130-139
  • DOI: 10.1016/j.humpath.2016.12.006.
  • Peer Reviewed
• [Journal Article] FOXO3a Expression Regulated by ERK Signaling is Inversely Correlated With Y-Box Binding Protein-1 Expression in Prostate Cancer. (2017)
  • Author(s): Imada K, Shiota M, Kuroiwa K, Sugimoto M, Abe T, Kohashi K, Yokomizo A, Eto M, Naito S, Oda Y.
  • Journal Title: Prostate. Volume: 77 Pages: 145-153
  • DOI: 10.1002/pros.23254.
  • Peer Reviewed
• [Journal Article] Phosphorylation of STAT3 in Undifferentiated Pleomorphic Sarcoma Is Correlated with a Favorable Prognosis. (2017)
  • Author(s): Bekki H, Kohashi K, Yamada Y, Iura K, Ishii T, Maekawa A, Otsuka H, Yamamoto H, Hakozaki M, Nabeshima K, Iwamoto Y, Oda Y.
  • Journal Title: Pathobiology. Volume: 印刷中 Pages: 印刷中
• [Journal Article] Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma. (2016)
  • Author(s): Satoh S, Takatori A, Ogura A, Kohashi K, Souzaki R, Kinoshita Y, Taguchi T, Hossain MS, Ohira M, Nakamura Y, Nakagawara A.
  • Journal Title: Sci Rep. Volume: 6 Pages: 32682
  • DOI: 10.1038/srep32682
  • Peer Reviewed
• [Journal Article] Prognostic significance of FOXM1 expression and antitumor effect of FOXM1 inhibition in synovial sarcomas. (2016)
  • Author(s): Maekawa A, Kohashi K, Kuda M, Iura K, Ishii T, Endo M, Nakatsura T, Iwamoto Y, Oda Y.
  • Journal Title: BMC Cancer. Volume: 16 Pages: 511
  • DOI: 10.1186/s12885-016-2542-4.
  • Peer Reviewed
• [Journal Article] Reclassification of rhabdoid tumor and pediatric undifferentiated/unclassified sarcoma with complete loss of SMARCB1/INI1 protein expression: three subtypes of rhabdoid tumor according to their histological features. (2016)
  • Author(s): Kohashi K, Tanaka Y, Kishimoto H, Yamamoto H, Yamada Y, Taguchi T, Iwamoto Y, Oda Y.
  • Journal Title: Mod Pathol. Volume: 29 Pages: 1232-1242
  • DOI: 10.1038/modpathol.2016.106.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epithelial to Mesenchymal Transition in Clear Cell Renal Cell Carcinoma with Rhabdoid Features. (2016)
  • Author(s): Sugimoto M, Kohashi K, Itsumi M, Shiota M, Abe T, Yamada Y, Kuroiwa K, Naito S, Oda Y.
  • Journal Title: Pathobiology. Volume: 83 Pages: 277-286
  • DOI: 10.1159/000445752.
  • Peer Reviewed
• [Journal Article] Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma. (2016)
  • Author(s): Ito T, Kohashi K, Yamada Y, Iwasaki T, Maekawa A, Kuda M, Hoshina D, Abe R, Furue M, Oda Y.
  • Journal Title: J Cancer. Volume: 7 Pages: 823-830
  • DOI: 10.7150/jca.14461.
  • Peer Reviewed
• [Journal Article] Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases. (2016)
  • Author(s): Yamada Y, Yamamoto H, Kohashi K, Ishii T, Iura K, Maekawa A, Bekki H, Otsuka H, Yamashita K, Tanaka H, Hiraki T, Mukai M, Shirakawa A, Shinnou Y, Jinno M, Yanai H, Taguchi K, Maehara Y, Iwamoto Y, Oda Y.
  • Journal Title: Histopathology. Volume: 69 Pages: 459-469
  • DOI: 10.1111/his.12943.
  • Peer Reviewed
• [Journal Article] Renal cell carcinoma with rhabdoid-like features lack intracytoplasmic inclusion bodies and show aggressive behavior. (2016)
  • Author(s): Sugimoto M, Kohashi K, Kuroiwa K, Abe T, Yamada Y, Shiota M, Imada K, Naito S, Oda Y.
  • Journal Title: Virchows Arch. Volume: 468 Pages: 357-367
  • DOI: 10.1007/s00428-015-1885-6.
  • Peer Reviewed
• [Journal Article] ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours. (2016)
  • Author(s): Yamamoto H, Yoshida A, Taguchi K, Kohashi K, Hatanaka Y, Yamashita A, Mori D, Oda Y.
  • Journal Title: Histopathology. Volume: 69 Pages: 72-83
  • DOI: 10.1111/his.12910.
  • Peer Reviewed
• [Journal Article] FOXM1 expression in rhabdomyosarcoma: a novel prognostic factor and therapeutic target. (2016)
  • Author(s): Kuda M, Kohashi K, Yamada Y, Maekawa A, Kinoshita Y, Nakatsura T, Iwamoto Y, Taguchi T, Oda Y.
  • Journal Title: Tumour Biol. Volume: 37 Pages: 5213-5223
  • DOI: 10.1007/s13277-015-4351-9.
  • Peer Reviewed
• [Journal Article] Activation of the Akt-mTOR and MAPK pathways in dedifferentiated liposarcomas. (2016)
  • Author(s): Ishii T, Kohashi K, Iura K, Maekawa A, Bekki H, Yamada Y, Yamamoto H, Nabeshima K, Kawashima H, Iwamoto Y, Oda Y.
  • Journal Title: Tumour Biol. Volume: 37 Pages: 4767-4776
  • DOI: 10.1007/s13277-015-4232-2.
  • Peer Reviewed
• [Presentation] Clinicopathological and molecular features of dedifferentiated liposarcoma with ossification: A comparative study with dedifferentiated liposarcoma without ossification and extraskeletal osteosarcoma (2017)
  • Author(s): Yamashita K, Kohashi K, Yamada Y, Oda Y, Toyokuni S
  • Organizer: Annual Meeting of the United States and Canadian Academy of Pathology
  • Place of Presentation: San Antonio, USA
  • Year and Date: 2017-03-07 – 2017-03-07
• [Presentation] Re-classification of rhabdoid tumor: three subtypes of rhabdoid tumor according to their histological features (2016)
  • Author(s): Kohashi K, Tanaka Y, Kishimoto H, Yamamoto H, Yamada Y, Kinoshita I, Taguchi T, Oda Y.
  • Organizer: 日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06 – 2016-10-06