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Role of ERM proteins and receptor-type tyrosine kinases in progression and metastasis of salivary gland carcinoma

Research Project

Project/Area Number 17K16921
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Otorhinolaryngology
Research InstitutionKyushu University

Principal Investigator

Hashimoto Kazuki  九州大学, 大学病院, 助教 (20707195)

Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords頭頸部腫瘍 / 唾液腺癌 / 浸潤転移 / 受容体型チロシンキナーゼ / 分子標的治療 / 免疫チェックポイント阻害剤 / 免疫チェックポイント阻害薬 / 頭頸部癌 / 遠隔転移 / 個別化治療 / 頭頸部外科学
Outline of Final Research Achievements

1. High ezrin expression was detected in 28.5% patients with salivary gland carcinoma (SGC). Concomitant expression of ezrin and HER2 correlated significantly with shorter overall survival as well as a high incidence of distant metastasis. 2. Although EGFR overexpression and gene copy number gain were detected in 77.8% and 16.7% patients with recurrent and/or metastatic SGC respectively, the effectiveness of EGFR-targeted therapy was unremarkable. 3. PD-L1 expression (CPS≧1) was detected in 68.5% patients with recurrent and/or metastatic SGC, with a particularly high rate of expression in high-grade histological types such as salivary duct carcinoma (SDC) or poorly differentiated carcinoma. Although the efficacy of PD-1 inhibitor therapy in recurrent and/or metastatic SGC was limited, there is a potential therapeutic effect in SDC patients with high PD-L1 expression.

Academic Significance and Societal Importance of the Research Achievements

頭頸部に発生する悪性腫瘍のうち約90%は扁平上皮癌であり、唾液腺癌をはじめとした腺癌系統の組織型を主体とする非扁平上皮癌の発生は比較的まれである。しかしながらその病理組織型は非常に多彩であり、各々の組織型についての分子生物学的特性は十分には解明されておらず、転移再発例に対する有効なレジメンも存在しないのが現状である。本研究では、唾液腺癌各組織型の浸潤転移、予後における、ezrinやHER2、EGFRといった分子異常の関与を明らかにした。また、転移再発唾液腺癌症例に対する、HER2、EGFR、PD-1等を標的とした新規治療における効果予測因子の解明を行った。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (38 results)

All 2022 2021 2020 2019 2018 2017 Other

All Journal Article (20 results) (of which Peer Reviewed: 20 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) Remarks (2 results)

  • [Journal Article] Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma2022

    • Author(s)
      HASHIMOTO KAZUKI、YASUMATSU RYUJI、KUGA RYOSUKE、HONGO TAKAHIRO、YAMAMOTO HIDETAKA、et al.
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 2 Pages: 981-989

    • DOI

      10.21873/anticanres.15558

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retrospective Study of Cisplatin/Carboplatin, 5-Fluorouracil Plus Cetuximab (EXTREME) for Advanced-stage Salivary Gland Cancer2022

    • Author(s)
      NAKANO TAKAFUMI、YASUMATSU RYUJI、HASHIMOTO KAZUKI、KUGA RYOSUKE、HONGO TAKAHIRO、et al.
    • Journal Title

      In Vivo

      Volume: 36 Issue: 2 Pages: 979-984

    • DOI

      10.21873/invivo.12790

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] p16 Overexpression and Rb Loss Correlate with High‐risk HPV Infection in Oropharyngeal Squamous Cell Carcinoma2021

    • Author(s)
      Jiromaru Rina、Yamamoto Hidetaka、Yasumatsu Ryuji、Hongo Takahiro、Nozaki Yui、Nakano Takafumi、Hashimoto Kazuki、Nakagawa Takashi、Oda Yoshinao
    • Journal Title

      Histopathology

      Volume: in print Issue: 3 Pages: 358-369

    • DOI

      10.1111/his.14337

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug-induced interstitial lung disease in recurrent and/or metastatic head and neck cancer patients treated with cetuximab and/or nivolumab2021

    • Author(s)
      Matsuo Mioko、Yasumatsu Ryuji、Masuda Muneyuki、Toh Satoshi、Wakasaki Takahiro、Hashimoto Kazuki、Uchi Ryutaro、Jiromaru Rina、Sato Kuniaki、Manako Tomomi、Nakagawa Takashi
    • Journal Title

      Oral Oncology

      Volume: 113 Pages: 105129-105129

    • DOI

      10.1016/j.oraloncology.2020.105129

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pan-tropomyosin receptor kinase immunoreactivity, ETV6-NTRK3 fusion subtypes, and RET rearrangement in salivary secretory carcinoma2021

    • Author(s)
      Yamamoto Hidetaka、Nozaki Yui、Sugii Azusa、Taguchi Kenichi、Hongo Takahiro、Jiromaru Rina、Sato Masanobu、Nakano Takafumi、Hashimoto Kazuki、Fujiwara Minako、Oda Yoshinao
    • Journal Title

      Human Pathology

      Volume: 109 Pages: 37-44

    • DOI

      10.1016/j.humpath.2020.11.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic Sequencing of Cancer-related Genes in Sinonasal Squamous Cell Carcinoma and Coexisting Inverted Papilloma2021

    • Author(s)
      UCHI RYUTARO、JIROMARU RINA、YASUMATSU RYUJI、YAMAMOTO HIDETAKA、HONGO TAKAHIRO、MANAKO TOMOMI、SATO KUNIAKI、HASHIMOTO KAZUKI、WAKASAKI TAKAHIRO、MATSUO MIOKO、NAKAGAWA TAKASHI
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 1 Pages: 71-79

    • DOI

      10.21873/anticanres.14752

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 結節性筋膜炎2021

    • Author(s)
      橋本和樹
    • Journal Title

      耳鼻と臨床

      Volume: 67 Pages: 124-127

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical outcome in recurrent and/or metastatic head and neck cancer patients after discontinuation of nivolumab monotherapy due to immune-related adverse events2020

    • Author(s)
      Yasumatsu Ryuji、Matsuo Mioko、Wakasaki Takahiro、Masuda Muneyuki、Takeuchi Toranoshin、Manako Tomomi、Jiromaru Rina、Uchi Ryutaro、Hashimoto Kazuki、Nakagawa Takashi
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 140 Issue: 12 Pages: 1043-1048

    • DOI

      10.1080/00016489.2020.1807601

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathologic Significance of EGFR Mutation and HPV Infection in Sinonasal Squamous Cell Carcinoma2020

    • Author(s)
      Hongo Takahiro、Yamamoto Hidetaka、Jiromaru Rina、Nozaki Yui、Yasumatsu Ryuji、Hashimoto Kazuki、Yoneda Reiko、Sugii Azusa、Taguchi Kenichi、Masuda Muneyuki、Nakagawa Takashi、Oda Yoshinao
    • Journal Title

      American Journal of Surgical Pathology

      Volume: 45 Issue: 1 Pages: 108-118

    • DOI

      10.1097/pas.0000000000001566

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between immune-related adverse events and long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab2020

    • Author(s)
      Matsuo M, Yasumatsu R, Masuda M, Toh S, Wakasaki T, Hashimoto K, Taura M, Uchi R, Nakagawa T.
    • Journal Title

      Oral Oncol

      Volume: in press Pages: 104525-104525

    • DOI

      10.1016/j.oraloncology.2019.104525

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] HPV-related sinonasal carcinoma: Clinicopathological features, diagnostic utility of p16 and Rb immunohistochemistry, and EGFR copy number alteration2020

    • Author(s)
      Jiromaru R, Yamamoto H, Yasumatsu R, Hongo T, Nozaki Y, Hashimoto K, Taguchi K, Masuda M, Nakagawa T, Oda Y.
    • Journal Title

      Am J Surg Pathol

      Volume: 44(3) Issue: 3 Pages: 305-315

    • DOI

      10.1097/pas.0000000000001410

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Monitoring the neutrophil-to-lymphocyte ratio may be useful for predicting the anticancer effect of nivolumab in recurrent or metastatic head and neck cancer2019

    • Author(s)
      Yasumatsu R, Wakasaki T, Hashimoto K, Nakashima K, Manako T, Taura M, Matsuo M, Nakagawa T
    • Journal Title

      Head Neck

      Volume: 41(8) Issue: 8 Pages: 2610-2618

    • DOI

      10.1002/hed.25737

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Parotid gland carcinoma: 32 years' experience from a single institute2019

    • Author(s)
      Nakano T, Yasumatsu R, Kogo R, Hashimoto K, Asai K, Ohga S, Yamamoto H, Nakashima T, Nakagawa T.
    • Journal Title

      Journal of Laryngology and Otology

      Volume: 133(7) Pages: 604-609

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 当院における中咽頭癌の治療成績 UICC/AJCC Cancer Staging 8thを勘案した後方視的解析2019

    • Author(s)
      若崎 高裕, 安松 隆治, 古後 龍之介, 橋本 和樹, 中川 尚志
    • Journal Title

      頭頸部外科

      Volume: 28巻3号 Pages: 271-276

    • NAID

      130007632071

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 頭頸部扁平上皮癌の遠隔転移に対して外科的切除を施行した症例の検討2019

    • Author(s)
      久我亮介, 橋本和樹, 内龍太郎, 中野貴史, 古後龍之介, 安松隆治, 田川哲三, 中川尚志
    • Journal Title

      頭頸部癌

      Volume: 45(3) Pages: 314-317

    • NAID

      130007744541

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The clinical value of serum squamous cell carcinoma antigens 1 and 2 in head and neck squamous cell carcinoma2019

    • Author(s)
      Yasumatsu Ryuji、Nakano Takafumi、Hashimoto Kazuki、Kogo Ryunosuke、Wakasaki Takahiro、Nakagawa Takashi
    • Journal Title

      Auris Nasus Larynx

      Volume: 46 Issue: 1 Pages: 135-140

    • DOI

      10.1016/j.anl.2018.07.010

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 高齢者頭頸部扁平上皮癌手術におけるPOSSUMを用いたリスク評価の検討(原著論文)2019

    • Author(s)
      益田昌吾, 中野貴史, 古後龍之介, 橋本和樹, 安松隆治, 中川尚志
    • Journal Title

      耳鼻と臨床

      Volume: 65 Pages: 11-17

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination of serum squamous cell carcinoma antigens 1 and 2 as potential diagnostic marker for sinonasal squamous cell carcinoma and inverted papilloma2018

    • Author(s)
      Yasumatsu Ryuji、Nakano Takafumi、Sato Masanobu、Jiroumaru Rina、Hashimoto Kazuki、Kogo Ryunosuke、Wakasaki Takahiro、Nakashima Torahiko、Nakagawa Takashi
    • Journal Title

      Head & Neck

      Volume: 40 Issue: 12 Pages: 2583-2589

    • DOI

      10.1002/hed.25351

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The treatment and outcome analysis of primary squamous cell carcinoma of the thyroid.2018

    • Author(s)
      Yasumatsu R, Sato M, Uchi R, Nakano T, Hashimoto K, Kogo R, Taura M, Matsuo M, Nakashima T, Nakagawa T.
    • Journal Title

      Auris Nasus Larynx.

      Volume: 45 Issue: 3 Pages: 553-557

    • DOI

      10.1016/j.anl.2017.07.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Concomitant expression of ezrin and HER2 predicts distant metastasis and poor prognosis of patients with salivary gland carcinomas.2017

    • Author(s)
      Hashimoto K, Hayashi R, Mukaigawa T, Yamazaki M, Fujii S.
    • Journal Title

      Human Pathology

      Volume: 印刷中 Pages: 110-119

    • DOI

      10.1016/j.humpath.2017.02.017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 唾液腺癌に対する免疫チェックポイント阻害薬の臨床効果に関する検討2021

    • Author(s)
      橋本和樹,安松隆治,松尾美央子,若崎高裕,次郎丸梨那,真子知美,山元英崇,久我亮介,益田宗幸,倉富勇一郎,瓜生英興,玉江昭裕,田浦政彦,竹内寅之進,吉田崇正,中川尚志
    • Organizer
      第45回日本頭頸部癌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 唾液腺腺様嚢胞癌におけるp16過剰発現は高リスク型ヒトパピローマウイルス感染の surrogate markerではない2019

    • Author(s)
      佐藤 方宣, 山元 英崇, 次郎丸 梨那, 橋本 和樹, 安松 隆治, 田口 健一, 益田 宗幸, 中川 尚志, 小田 義直
    • Organizer
      第43回日本頭頸部癌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 鼻副鼻腔癌におけるHPV感染とEGFR遺伝子コピー数増加の予後に及ぼす影響2019

    • Author(s)
      次郎丸 梨那, 山元 英崇, 安松 隆治, 本郷 貴大, 野崎 優衣, 橋本 和樹, 田口 健一, 益田 宗幸, 中川 尚志, 小田 義直
    • Organizer
      第43回日本頭頸部癌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 頭頸部原発横紋筋肉腫の臨床病理学的検討2018

    • Author(s)
      橋本和樹,安松隆治,佐藤方宣,山元英崇,古賀友紀,馬場英司,大賀才路,中川尚志
    • Organizer
      第42回日本頭頸部癌学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 顔面神経麻痺および急性感音難聴を初発症状とした小児脳幹部神経膠腫の2例2018

    • Author(s)
      久我亮介,内龍太郎,濵田康宏,門屋亮,橋本和樹
    • Organizer
      第119回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 反回神経麻痺を来した巨大甲状腺嚢胞の一例2018

    • Author(s)
      佐藤方宣、久我亮介、橋本和樹
    • Organizer
      第302回 日本耳鼻咽喉科学会山口県地方部会
    • Related Report
      2018 Research-status Report
  • [Presentation] 下顎骨区域切除における術中迅速骨髄捺印細胞診の有用性について2017

    • Author(s)
      橋本和樹,安松隆治,古後龍之介,中野貴史,内龍太郎,佐藤方宣,山元英崇,中川尚志
    • Organizer
      第41回日本頭頸部癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 当科における甲状腺未分化癌の臨床学的検討2017

    • Author(s)
      内龍太郎, 安松隆治, 古後龍之介, 橋本和樹, 中野貴史, 中川尚志
    • Organizer
      第118回日本耳鼻咽喉科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頸部操作にて摘出しえた食道神経鞘腫の1例2017

    • Author(s)
      松永啓秀, 安松隆治, 佐藤方宣, 久我亮介, 中野貴史, 古後龍之介, 橋本和樹, 中川尚志
    • Organizer
      第118回日本耳鼻咽喉科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] HPV陽性中咽頭癌におけるHPV感染様式に基づいた臨床病理学的検討2017

    • Author(s)
      中野貴史, 安松隆治, 山元英崇, 佐藤方宣, 次郎丸梨那, 古後龍之介, 橋本和樹,中川尚志
    • Organizer
      第118回日本耳鼻咽喉科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 唾液腺癌におけるPD-L1発現は予後不良因子である2017

    • Author(s)
      向川卓志、林隆一、橋本和樹、鵜久森徹、羽藤直人、藤井誠志
    • Organizer
      第41回日本頭頸部癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頭頸部化学放射線療法に対する栄養管理と治療完遂率に関する検討2017

    • Author(s)
      古後龍之介、安松隆治、中野貴史、橋本和樹、中川尚志
    • Organizer
      第41回日本頭頸部癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頭頸部癌の遠隔転移に対して外科的切除を施行した症例の検討2017

    • Author(s)
      久我亮介、橋本和樹、内龍太郎、中野貴史、古後龍之介、安松隆治、中川尚志
    • Organizer
      第41回日本頭頸部癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 鼻・副鼻腔癌,内反性乳頭腫におけるSCCA1, SCCA2測定の有用性2017

    • Author(s)
      安松隆治、内龍太郎、中野貴史、橋本和樹、古後龍之介、中川尚志
    • Organizer
      第41回日本頭頸部癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 副咽頭間隙腫瘍の2例2017

    • Author(s)
      久我亮介、橋本和樹、内龍太郎、菊池奈美
    • Organizer
      第297回 日本耳鼻咽喉科学会山口県地方部会
    • Related Report
      2017 Research-status Report
  • [Presentation] 下咽頭・喉頭全摘後に遊離前外側大腿皮弁を用いて管状再建を行った一例2017

    • Author(s)
      内龍太郎、久我亮介、橋本和樹、吉田聖
    • Organizer
      第299回 日本耳鼻咽喉科学会山口県地方部会
    • Related Report
      2017 Research-status Report
  • [Remarks] 九州大学大学院医学研究院 耳鼻咽喉科学教室 / 九州大学病院 耳鼻咽喉・頭頸部外科

    • URL

      https://www.qent.med.kyushu-u.ac.jp/group/research.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 九州大学大学院医学研究院 耳鼻咽喉科学教室

    • URL

      http://www.qent.med.kyushu-u.ac.jp/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2023-01-30  

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