Molecular and clinicopathological study of mammary analogue secretory carcinoma (MASC)

• Project/Area Number: 16K11467
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Aichi Gakuin University
• Principal Investigator: MIYABE Satoru 愛知学院大学, 歯学部, 講師 (40534582)
• Co-Investigator(Kenkyū-buntansha): 下郷 和雄 愛知学院大学, 歯学部, 非常勤講師 (00158966)
• Project Period (FY): 2016-10-21 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 臨床病理学 / 唾液腺腫瘍 / 分子病理学的解析 / 分泌癌 / 遺伝子変異 / 唾液腺悪性腫瘍 / FISH / 融合遺伝子 / 上皮癌 / 遺伝子異常 / Secretory carcinoma (SC) / ETV6関連融合遺伝子 / ETV6-NTRK3融合遺伝子 / 唾液腺癌

Outline of Final Research Achievements

MASC was a similar secretory carcinoma of the mammary gland, but it was classified as a new unit on WHO (4th ed), and now as secretory carcinoma (SC). 38 cases of secretory carcinoma were collected. It was reported that ETV6-NTRK3 was a molecular pathological feature of this tumor, but then RET, MET, MAML3 was used as the ETV6 partner gene. In addition, cases in which novel fusion genes such as VIM-RET and EGFR-SEPT14 are recognized have also been reported. ETV6-NTRK3 fusion gene was found in 35 out of 38 cases, and ETV6-RET in 1, ETV6-MET in 1, and ETV6-MAML3 in 1 case. We reported that the ETV6-X fusion was assumed including cases with strong fibrosis and necrosis in secretory carcinoma, and it was reported that these cases harbored ETV6-RET. Among the cases collected we also found that two cases of ETV6-MET and ETV6-MAML3 each other also showed strong fibrosis and necrosis, we reported these results at the 16th cytology workshop held by the Aichi Clinical Cytology Society 2019.

Academic Significance and Societal Importance of the Research Achievements

本研究では、唾液腺分泌癌においてETV6-NTRK3以外の融合遺伝子の存在を収集症例においても明らかにした。研究目的の1つであった新たな関連遺伝子異常の検出が可能になったことから、「組織像が分泌癌であるがETV6遺伝子異常が検出されない症例」の存在が唾液腺腫瘍診断医を悩ます機会が減少すると考える。本研究は分泌癌から独立疾患単位として認められた分泌癌の診断精度の向上にもつながると考えられる。surrogate markerとしての遺伝子異常解析が、唾液腺分泌癌の診断精度を高めることを明らかにした点に学術的意義がある考える。

Research Products

• [Int'l Joint Research] Mund-, Kiefer- und Gesichtschirurgie/der Universit Mnchen.(Germany)
• [Journal Article] Changes in Oral Microbial Profiles Associated With Oral Squamous Cell Carcinoma vs Leukoplakia (2019)
  • Author(s): Kengo Hashimoto, Dai Shimizu, Sho Hirabayashi, Sei Ueda, Satoru Miyabe, Ichiro Oh-Iwa, Toru Nagao, Kazuo Shimozato, Shuji Nomoto
  • Journal Title: J Investig Clin Dent . Volume: 10 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Association between p62 expression and clinicopathological characteristics in oral leukoplakia. (2019)
  • Author(s): T. Yoshida, T. Terabe, H. Nagai, F. Uchida, S. Hasegawa, T. Nagao, S. Miyabe, N. Ishibashi‐Kanno, K. Yamagata, E. Warabi, M. Gosho, T. Yanagawa, H. Bukawa
  • Journal Title: Clinical and Experimental Dental Research Volume: 5 Issue: 4 Pages: 389-397
  • DOI: 10.1002/cre2.193
  • NAID: 120007133181
  • Peer Reviewed / Open Access
• [Journal Article] Adenoid Cystic Carcinoma With Sialolithiasis of the Left Submandibular Gland: A Case Report and Literature Review (2018)
  • Author(s): Miyabe Satoru、Ishibashi Kenichiro、Saida Kosuke、Fujiyoshi Yukio、Fukano Hideo、Ueda Kaori、Ueda Sei、Watanabe Satoshi、Nagao Toru
  • Journal Title: International Journal of Surgical Pathology Volume: 27 Issue: 3 Pages: 305-310
  • DOI: 10.1177/1066896918814304
  • Peer Reviewed / Open Access
• [Journal Article] p53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia (2017)
  • Author(s): Nagao T, Warnakulasuriya S, Sakuma H, et al
  • Journal Title: J Oral Pathol Med Volume: 46 Issue: 5 Pages: 346-352
  • DOI: 10.1111/jop.12498
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 耳下腺原発混成癌の2症例 (2019)
  • Author(s): 草深 公秀, 鬼塚 哲郎, 宮部 悟, 石橋 謙一郎
  • Organizer: 日本唾液腺学会
• [Presentation] 非常に稀な唾液腺原発混成癌の2症例 (2019)
  • Author(s): 草深 公秀, 宮部 悟, 石橋 謙一郎, 中島 孝, 杉野 隆
  • Organizer: 日本病理学会
• [Presentation] 耳下腺原発混成癌2例の病理学的解析 (2019)
  • Author(s): 草深 公秀, 鬼塚 哲郎, 上條 朋之, 宮部 悟, 石橋 謙一郎, 濱田 宜子, 森田 浩太朗, 向川 卓志, 西谷 友樹雄, 飯田 善幸, 中島 孝, 寺田 忠史
  • Organizer: 頭頸部癌学会
• [Presentation] Salivary gland carcinoma with gene rearrangements. (2018)
  • Author(s): Satoru Miyabe, et al.
  • Organizer: 43th AOMSI, Chennai, 2018
  • Int'l Joint Research / Invited
• [Presentation] Salivary gland carcinoma with gene alterations. (2018)
  • Author(s): Ishibashi Kenichiro, Satoru Miyabe, et al.
  • Organizer: 23rd ICOMS, Hong Cong, 2018
  • Int'l Joint Research / Invited
• [Presentation] 術後再発により mammary analogue secretory carcinoma と診断し得 た耳下腺腫瘍の 1 例 (2017)
  • Author(s): 飯田 俊、山口 岳彦、小野 祐子、河合 繁夫、宮部 悟、今田 浩生、 藤井 晶子、伴 慎一、上田 善彦
  • Organizer: 第106回日本病理学会総会
  • Place of Presentation: 京王プラザ
  • Year and Date: 2017-04-27
• [Presentation] 唾液腺腫瘍の細胞診:新WHO分類を踏まえて 唾液腺分泌癌の細胞学的特徴と鑑別診断 (2017)
  • Author(s): 浦野誠、樋口 佳代子, 宮部 悟, 長尾 俊孝, 黒田 誠, 宮部悟
  • Organizer: 日本臨床細胞学会
  • Invited
• [Presentation] 術後再発によりmammary analogue secretory carcinomaと診断し得た耳下腺腫瘍の1例 (2017)
  • Author(s): 飯田 俊、 山口 岳彦, 小野 祐子, 河合 繁夫, 宮部 悟, 今田 浩生, 藤井 晶子, 伴 慎一, 上田 善彦
  • Organizer: 日本病理学会
• [Book] 唾液腺細胞診ミラノシステム （原書名：The Milan System for Reporting Salivary Gland Cytopathology） (2019)
  • Author(s): 樋口佳代子，浦野誠，宮部悟ほか
  • Total Pages: 155
  • Publisher: 株式会社 金芳堂
  • ISBN: 9784765317863
• [Book] 病理診断プラクティス『唾液腺・歯原性腫瘍』「粘表皮癌」 (2019)
  • Author(s): 宮部 悟ほか（共著）
  • Publisher: 中山書店
• [Book] 「唾液腺細胞診報告様式ミラノシステム」日本語訳 第8章”Chapter 8: Ancillary Studies for Salivary Gland Cytology.” (2019)
  • Author(s): 宮部 悟ほか（共著）
  • Publisher: 金芳堂
• [Remarks] 愛知学院大学 教員情報
  • URL: http://aris.agu.ac.jp/aiguhp/KgApp?kyoinId=ymdegkodggy