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Study on cytological diagnosis of mesothelioma: Application of genetic alterations to pathological diagnosis system

Research Project

Project/Area Number 19K07451
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionFukuoka University

Principal Investigator

Nabeshima Kazuki  福岡大学, 医学部, 教授 (40189189)

Co-Investigator(Kenkyū-buntansha) 濱崎 慎  福岡大学, 医学部, 准教授 (90412600)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsmesothelioma / BAP1 / MTAP / CDKN2A/p16 / NF2 / FISH / cytology / 中皮腫 / 細胞診 / 免疫組織化学
Outline of Research at the Start

本研究は、組織での浸潤の証明にこだわらず、細胞診という臨床に即した手段で、腫瘍抑制遺伝子のホモ/ヘミ欠失あるいは変異による蛋白発現欠失を検出し、細胞の腫瘍性を証明しようという試みである。すでにこれまでの諸家による研究によって、スクリーニングにおいて中皮腫を疑うべき形態学的特徴はほぼ確立している。それをさらに遺伝子変異あるいはそれに関連する変化によって確定させ、早期診断、早期の治療開始に導こうという試みである。さらにそれをFISH施行可能施設(基幹施設)と免疫染色のみを施行できる施設に分けて、それぞれで最適の診断手段(遺伝子変異関連)の組み合わせを検討し、提唱するというものである。

Outline of Final Research Achievements

About 80% of pleural mesothelioma (PM) start with pleural effusions, and thus detection of tumor cells by effusion cytology is important. However, discriminating PM cells from reactive mesothelial cells (RMC) is sometimes challenging. This study revealed that application of genomic-based ancillary assays to effusion cytology (cell blocks) enables to determine neoplastic nature of PM cells, which distinguishes PM cells from RMC. Moreover, application of FISH assays increases sensitivity of discrimination of PM cells from RMC.

Academic Significance and Societal Importance of the Research Achievements

本研究にて、中皮腫の遺伝子変異に基づいたアッセイ(BAP1免染、MTAP免染、CDKN2A/p16 FISH)は組織標本のみならず細胞診標本(セルブロック)にも応用可能で、特にその併用(組み合わせ)によって高率に、対象となる中皮細胞の腫瘍性を示すことが明らかとなった。更にNF2 FISHを組み合わせると特異度100%はそのままに100%近い診断感度をもたらすことができる。高齢者における中皮腫発生が増え、免疫チェックポイント阻害薬併用による治療が第一選択となることを考慮すると、この細胞診による診断の学術的・社会的意義は大きい。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (31 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Chicago(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma2021

    • Author(s)
      Kinoshita Y, Hamasaki M, Matsumoto S, Yoshimura M, Sato A, Tsujimura T, Kamei T, Kawahara K, Iwasaki A, Nabeshima K
    • Journal Title

      Cancer Cytopathology

      Volume: 129 Issue: 7 Pages: 526-536

    • DOI

      10.1002/cncy.22409

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Short 57 kb CDKN2A FISH probe effectively detects short homozygous deletion of the 9p21?locus in malignant pleural mesothelioma2021

    • Author(s)
      Oyama Y, Hamasaki M, Matsumoto S, Sato A, Tsujimura T, Nabeshima K
    • Journal Title

      Oncology Letters

      Volume: 22 Issue: 6 Pages: 813-813

    • DOI

      10.3892/ol.2021.13074

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 新WHO胸部腫瘍分類におけるupdate-胸膜中皮腫におけるupdate.2021

    • Author(s)
      鍋島一樹、濵﨑慎
    • Journal Title

      病理と臨床

      Volume: 39(7) Pages: 679-686

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 悪性胸膜中皮腫の病理診断-中皮腫関連遺伝子変異の診断応用.2021

    • Author(s)
      濵﨑慎, 鍋島一樹.
    • Journal Title

      診断病理

      Volume: 38 Pages: 126-135

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 治療方針を変える病理所見-8.胸膜(悪性中皮腫)2021

    • Author(s)
      鍋島一樹、濵﨑慎
    • Journal Title

      病理と臨床 臨時増刊号

      Volume: 39 Pages: 58-65

    • Related Report
      2021 Annual Research Report
  • [Journal Article] HEG1, BAP1, and MTAP Are Useful in Cytologic Diagnosis of Malignant Mesothelioma With Effusion.2021

    • Author(s)
      Hiroshima K, Wu D, Hamakawa S, Tsuruoka S, Ozaki D, Orikasa H, Hasegawa M, Koh E, Sekine Y, Yonemori Y, Nabeshima K, Tsuji S, Miyagi Y, Imai K.
    • Journal Title

      Diagn Cytopathol

      Volume: 49 Issue: 5 Pages: 622-632

    • DOI

      10.1002/dc.24475

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases.2021

    • Author(s)
      Chapel DB, Schulte JJ, Absenger G, Attanoos R, Brcic L, Butnor KJ, Chirieac L, Churg A, Galateau-Sallé F, Hiroshima K, Hung YP, Kindler H, Krausz T, Marchevsky A, Mino-Kenudson M, Mueller J, Nabeshima K, Turaga K, Walts AE, Husain AN.
    • Journal Title

      Mod Pathol

      Volume: 34 Issue: 2 Pages: 380-395

    • DOI

      10.1038/s41379-020-00688-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful for the diagnosis of malignant pleural mesothelioma.2020

    • Author(s)
      Kinoshita Y, Hamasaki M, Yoshimura M, Matsumoto S, Iwasaki A, Nabeshima K
    • Journal Title

      Mod Pathol

      Volume: 33 Issue: 2 Pages: 235-244

    • DOI

      10.1038/s41379-019-0309-6

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] MTAP immunohistochemistry is an accurate and reproducible surrogate for CDKN2A fluorescence in situ hybridization in diagnosis of malignant pleural mesothelioma.2020

    • Author(s)
      Chapel DB, Schulte JJ, Berg K, Churg A, Dacic S, Fitzpatrick C, Galateau-Salle F, Hiroshima K, Krausz T, Le Stang N, McGregor S, Nabeshima K, Husain AN.
    • Journal Title

      Mod Pathol

      Volume: 33 Issue: 2 Pages: 245-254

    • DOI

      10.1038/s41379-019-0310-0

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical feature of diagnostic challenging cases for pleural biopsy in patient with malignant pleural mesothelioma.2020

    • Author(s)
      Hashimoto M, Sato A, Kuroda A, Nakamura A, Nakamichi T, Kondo N, Yuki M, Nabeshima K, Tsujimura T, Hasegawa S.
    • Journal Title

      Gen Thorac Cardiovasc Surg.

      Volume: - Issue: 8 Pages: 820-827

    • DOI

      10.1007/s11748-020-01295-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Utility of highly expressed EZH2 in pleural effusion cytology for the diagnosis of mesothelioma2020

    • Author(s)
      Yoshimura M, Hamasaki M, Kinoshita Y, Matsumoto S, Sato A, Tsujimura T, Iwasaki A, Nabeshima K
    • Journal Title

      Pathology International

      Volume: 70 Issue: 10 Pages: 831-833

    • DOI

      10.1111/pin.12990

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic‐based ancillary assays offer improved diagnostic yield of effusion cytology with potential challenges in malignant pleural mesothelioma2020

    • Author(s)
      Kinoshita Y, Hamasaki M, Matsumoto S, Yoshimura M, Sato A, Tsujimura T, Kamei T, Kawahara K, Nabeshima K
    • Journal Title

      Pathology International

      Volume: 70 Issue: 9 Pages: 671-679

    • DOI

      10.1111/pin.12973

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] 免疫組織化学-実践的な診断・治療のために-11.中皮腫.2020

    • Author(s)
      鍋島一樹、濵﨑慎、木下義晃、吉村雅代、松本慎二.
    • Journal Title

      病理と臨床

      Volume: 38 Pages: 142-148

    • Related Report
      2019 Research-status Report
  • [Journal Article] Cytoplasmic MTAP expression loss detected by immunohistochemistry correlates with 9p21 homozygous deletion detected by FISH in pleural effusion cytology of mesothelioma.2019

    • Author(s)
      Hamasaki M, Kinoshita Y, Yoshimura M, Matsumoto S, Kamei T, Hiroshima K, Sato A, Tsujimura T, Kawahara K, Nabeshima K.
    • Journal Title

      Histopathology

      Volume: 75 Issue: 1 Pages: 153-155

    • DOI

      10.1111/his.13872

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Morphological difference between pleural mesothelioma cells in effusion smears with either BAP1 loss or 9p21 homozygous deletion and reactive mesothelial cells without the gene alterations.2019

    • Author(s)
      Matsumoto S, Hamasaki M, Kinoshita Y, Kamei T, Kawahara K, Nabeshima K.
    • Journal Title

      Pathol Int

      Volume: 69 Issue: 11 Pages: 637-645

    • DOI

      10.1111/pin.12862

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 胸膜中皮腫病理診断のupdate - 2021 WHO分類における変更点など2021

    • Author(s)
      鍋島 一樹, 濱崎 慎.
    • Organizer
      第26回日本肺癌学会学術集会, 2021.11.26-28, 横浜.
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 胸膜/腹膜 中皮腫とその鑑別疾患2021

    • Author(s)
      鍋島 一樹
    • Organizer
      国際病理アカデミー(IAP)日本支部 病理学教育セミナー(スライドセミナー)2021.11.16-12.5.
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The Usefulness of NF2 Fluorescence In Situ Hybridization in the Diagnosis of Mesothelioma in Tissue and Cytological Specimens.2020

    • Author(s)
      Kinoshita Y, Hamasaki M, Matsumoto S, Yoshimura M, Sato A, Tsujimura T, Iwasaki A, Nabeshima K.
    • Organizer
      109th Annual Meeting of United States & Canadian Academy of Pathology
    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] NF2 fluorescence in situ Hhybridization is effectively separate mesothelioma from reactive mesothelial proliferations.2020

    • Author(s)
      Hamasaki M, Kinoshita Y, Matsumoto S, Sato A, Tsujimura T, Iwasaki A, Nabeshima K.
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 中皮腫診断の基礎と免疫染色・FISH.2019

    • Author(s)
      鍋島一樹
    • Organizer
      第8回神戸免疫組織診断セミナー(第8回いむーのセミナー)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Cytologic diagnosis of mesothelioma. Update with use of ancillary assays based on genetical changes in mesothelioma.2019

    • Author(s)
      Nabeshima K, Hamasaki M, Kinoshita Y, Matsumoto S, Sato A, Tsujimura T, Kawahara K, Hiroshima K, Kamei T.
    • Organizer
      The 42nd European Congress of Cytology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 生検および細胞診におけるNF2 FISH:悪性胸膜中皮腫と良性中皮過形成の鑑別における有用性.2019

    • Author(s)
      木下義晃, 濱崎慎, 吉村雅代, 松本慎二, 岩崎昭憲, 鍋島一樹.
    • Organizer
      第1回日本石綿・中皮腫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 胸水細胞診を用いた悪性胸膜中皮腫診断プロセスと問題点. ワークショップ6. 体腔液の細胞診の進化.2019

    • Author(s)
      濵﨑 慎, 松本 慎二, 木下義晃, 亀井敏昭, 鍋島一樹.
    • Organizer
      第60回日本臨床細胞学会春期大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Sarcomatoid mesotheliomaのアップデート. ワークショップ14. 胸部腫瘍性疾患のアップデート.2019

    • Author(s)
      鍋島一樹、濵﨑慎、木下義晃、吉村雅代、松本慎二、佐藤鮎子、辻村亨、亀井敏昭、岩崎昭憲.
    • Organizer
      第108回日本病理学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 生検と細胞診による中皮腫診断:我々の戦略と現状.2019

    • Author(s)
      鍋島一樹
    • Organizer
      第52回日本胸部外科学会 九州地方会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 中皮腫診断 update:細胞診でどこまでせまれるか?!2019

    • Author(s)
      鍋島一樹.
    • Organizer
      第35回日本臨床細胞学会九州連合会学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Malignant pleural mesothelioma: histologic and cytologic diagnosis based on genetic alterations.2019

    • Author(s)
      Nabeshima K.
    • Organizer
      Symposium: Translational Research on Metabolic and Inflammatory Diseases and Cancer.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 中皮腫の細胞診診断 update-中皮腫の遺伝子変異に基づく補助診断法.2019

    • Author(s)
      濵崎慎,木下義晃,松本慎二,佐藤鮎子,辻村 亨,河原邦光,廣島健三, 亀井敏昭,鍋島一樹.
    • Organizer
      第58回日本臨床細胞学会秋期大会
    • Related Report
      2019 Research-status Report
  • [Book] Malignant Pleural Mesothelioma. Advances in Pathogenesis, Diagnosis, and Treatments2021

    • Author(s)
      Nabeshima K, Hamasaki M, Kinoshita Y, Yoshimura M, Matsumoto S.
    • Total Pages
      352
    • Publisher
      SpringerLink
    • ISBN
      9789811591587
    • Related Report
      2020 Research-status Report
  • [Remarks] 悪性腹膜中皮腫の予後推測モデルの確立に関する国際共同研究

    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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