| Project/Area Number |
16K11718
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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 |
Surgical dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Michikawa Chieko 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (00622648)
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| Co-Investigator(Kenkyū-buntansha) |
鵜澤 成一 東京医科歯科大学, 歯学部附属病院, 講師 (30345285)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 被膜外浸潤 / 扁平上皮癌 / TP53 / 次世代シーケンス / 頭頚部癌 / 臨床試験 / 口腔癌 / NRG / 頸部リンパ節転移 / 頭頚部がん / 口腔がん / 第2相試験 / RTOG / 頭頸部癌 |
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| Outline of Final Research Achievements |
We observed that mutation of the TP53 gene was the most common event in oral squamous cell carcinomas with extracapsular spread (ECS) of lymph node metastasis. The frequency of TP53 mutation in ECS-positive tumors was higher compared with ECS-negative tumors and wild-type TP53 was highly represented in pN0 tumors. ECS-positive patients had the highest proportion of high-risk TP53 mutations. There were no significant difference in allele frequency between primary tumors and lymph node metastasis with ECS.
Using resected specimens from enrolled patients on randomized phase II clinical trial which assessed new adjuvant therapy, we found TP53 status to be predictive of outcome to cisplatin- and docetaxel-based combination bio-chemoradiotherapy in patients with pathologically high-risk human papillomavirus-negative head and neck squamous cell carcinoma. Pathologically high-risk factors included positive margin and/or ECS-positive and/or two or more positive nodes.
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| Academic Significance and Societal Importance of the Research Achievements |
頭頚部癌において、被膜外浸潤を呈する患者を含む病理組織学的高リスク患者群に対する術後補助療法として、世界標準治療が定められているが、特に、副作用、および、遠隔転移の減少を目指し、さらなる改善が必要であり、臨床試験が施行されている。これに伴い、治療法の選択を補助するバイオマーカーの探索は重要であると考え、我々は頭頚部癌において最も頻度の高い変異であるTP53遺伝子変異と被膜外浸潤、そして、臨床試験登録患者群の経過との関連性に注目して解析した。
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