| Project/Area Number |
17K08705
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
多田 雄一郎 国際医療福祉大学, 医学部, 准教授 (70292430)
山崎 一人 帝京大学, 医学部, 教授 (60302519)
平井 秀明 東京医科大学, 医学部, 助教 (00770744)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 唾液腺癌 / バイオマーカー / 予後 / 唾液腺導管癌 / HER2 / AR / TP53 / 人体病理学 / FOXA1 |
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| Outline of Final Research Achievements |
In salivary duct carcinoma (SDC), a histological analysis revealed that prominent nuclear pleomorphism, high mitoses, high poorly differentiated clusters, and vascular invasion were poor prognostic factors. Histologic risk stratification model, based on above 4 prognostically relevant parameters, could effectively predict patient survival. Immunohistochemically, low AR, p53-extreme negative/positive, low FOXA1, and high adipophilin expression were associated with poor prognosis. Furthermore, patients with SDC harboring TP53 mutations showed shorter survival rate. We categorized All SDCs into four main subtypes pursuant to a combination of the expression of AR, HER2, and Ki-67. Consequently, patients with ‘apocrine A’ displayed a better progression-free survival than those with any other subtypes. Based on this classification, we conducted phase II trial of anti-AR and HER2 therapies in patients with AR- and HER2-positive SDCs. These therapies demonstrated high efficacy.
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| Academic Significance and Societal Importance of the Research Achievements |
唾液腺導管癌（SDC）は比較的稀な組織型のため少数例での検討しかされておらず、本研究のような大規模なSDCの解析は世界的にも類を見ない。SDCの各種バイオマーカーの発現様式や遺伝子異常と臨床病理学的特徴との関連を明らかにすることで、実臨床において正確な予後予測や適切な治療法選択に寄与すると考えられる。また、我々が行ったSDCに対する複合アンドロゲン遮断療法と抗HER2療法は共に、世界初の前向き臨床試験であり、その成果は米国NCCNガイドライン最新版に反映されている。これはSDCに対する個別化治療を確立し、当該患者の予後やQOLの改善に繋がる成果であり、大変意義深い。
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