| Project/Area Number |
17K10567
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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 |
General surgery
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| Research Institution | Research Institute for Clinical Oncology, Saitama Cancer Center (2019)
Japanese Foundation for Cancer Research (2017-2018) |
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Principal Investigator |
Horii Rie 埼玉県立がんセンター(臨床腫瘍研究所), 病院 病理診断科, 医長 (20446272)
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| Co-Investigator(Kenkyū-buntansha) |
秋山 太 公益財団法人がん研究会, がん研究所 病理部, 臨床病理担当部長 (50222550)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 腫瘍内不均質性 / HER2 / 乳癌 / Gene-protein assay / 抗HER2療法 / 効果予測因子 / 予後因子 / 癌 / 病理学 |
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| Outline of Final Research Achievements |
We investigated the relationships between various indicators for HER2 intratumoral heterogeneity (ITH) and clinical course in HER2-positive breast cancer patients, treated with neoadjuvant trastuzumab and chemotherapy. The degree of HER2-ITH was quantified using HER2 gene copy number and protein expression of each cancer cell assessed by gene-protein assay slides of pretherapeutic biopsy specimens. Achievement of pCR for neoadjuvant treatments showed positive relationships to the mean gene copy number (P < 0.001), the mean protein category (P < 0.001) and the proportion of gene-amplified and protein-positive tumor cells (P < 0.001) and negative relationships to the CV of protein category (P < 0.001) and the proportion of gene-amplified but protein-negative tumor cells (P = 0.002). The diagnostic models, created by combining clinicopathological factors and the ITH indicators, showed excellent diagnostic ability for therapeutic effect of trastuzumab-based treatments.
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| Academic Significance and Societal Importance of the Research Achievements |
ITHは遺伝子型の多様性に起因するもの(genetic ITH)と遺伝子型は同一だが表現型が多様なもの(non-genetic ITH)とに分けられる。本研究の特色はGPAを用いて遺伝子とタンパク両方を評価しITHを定量化した点にある。遺伝子シグナル数の平均はgenetic ITH、遺伝子増幅がみられるがタンパク低発現の癌細胞の割合はnon-genetic ITH、遺伝子増幅かつタンパク過剰発現の癌細胞の割合は両者を組み合わせたITHを示し、夫々がトラスツズマブを含む薬物療法の効果と関連していた。HER2-ITHは抗HER2療法の効果予測に有用で、乳癌症例の治療方針決定に際し評価すべきである。
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