Association of Nerve growth factor and Immune escape for Perineural invasion in Adenoid cystic carcinoma

• Project/Area Number: 16K20232
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: The University of Tokyo
• Principal Investigator: Kobayashi Kenya 東京大学, 医学部附属病院, 登録研究医 (80648311)
• Research Collaborator: Ando Mizuo ; Kondo Kenzi ; Yoshida Masahumi ; Saito Yuki ; Omura Go
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 腺様嚢胞癌 / MYB-NFIB癒合遺伝子 / 免疫逃避機構 / PDL1 / 癒合遺伝子 / PD-L1 / NTRK / 神経周囲浸潤 / 神経栄養因子 / PD-Ｌ1

Outline of Final Research Achievements

In this study, we analyzed molecular biological features of 37 adenoid cystic carcinoma tumor specimens. PD-L1 expression analysis by immunostaining revealed 21% cases are overexpressed PD-L1(positive cell >10%). PD-L1 overexpression was significantly associated with poor local control rate. In FISH analysis, MYB-NFIB fusion gene were detected in 51% cases. To detected novel NTRK (coding Trk recepter) fusion gene, we performed RNA sequencing for Nerve Growth factor/TrkA receptor overexpress tumor, however there were no detection of novel fusion gene. Gene expression analysis of RNA sequencing, high frequent mutation was SP1, CEP57, DST, FGFR2, KANK1, EPCAM, NOTCH1.

Academic Significance and Societal Importance of the Research Achievements

腺様嚢胞癌は外科治療以外に有効治療がない難治性腫瘍である。その理由として、希少癌であること、神経周囲浸潤・遠隔転移を来しやすいこと、有効な薬剤がないことなどが上げられており、腫瘍の分子生物学的特徴の解明は急務である。本研究では、腺様嚢胞癌の免疫逃避機構の関連、予後との相関を明らかにし、発癌に関与する融合遺伝子も検討した。さらに、変異頻度が高い遺伝子を同定したことで、治療開発に役立つ可能性がある。

Research Products

• [Journal Article] All-Exon TP53 Sequencing and Protein Phenotype Analysis Accurately Predict Clinical Outcome after Surgical Treatment of Head and Neck Squamous Cell Carcinoma. (2019)
  • Author(s): 1.Kobayashi K, Yoshimoto S, Matsumoto F, Ando M, Murakami N, Omura G, Fukasawa M, Matsumoto Y, Matsumura S, Akamatsu M, Hiraoka N, Eigitsu R, Mori T.
  • Journal Title: Ann Surg Oncol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Impact of Surgical Margin in Skull Base Surgery for Head and Neck Sarcomas. (2018)
  • Author(s): 2.Kobayashi K, Matsumoto F, Miyakita Y, Mori T, Shimoi T, Murakami N, Yoshida A, Arakawa A, Omura G, Fukawasa M, Matsumoto Y, Matsumura S, Itami J, Narita Y, Yoshimoto S.
  • Journal Title: J Neurol Surg B. Volume: 79(5) Pages: 437-444
  • Peer Reviewed
• [Journal Article] Impact of microscopic orbital periosteum invasion in orbital preservation surgery. (2017)
  • Author(s): Kobayashi K, Mori T, Matsumoto F, Murakami N, Teshima M, Fukasawa M, Matsumoto Y, Matsumura S, Itami J, Asai M, Yoshimoto S.
  • Journal Title: Jpn J Clin Oncol. Volume: 47 Issue: 4 Pages: 321-327
  • DOI: 10.1093/jjco/hyw207
  • Peer Reviewed
• [Journal Article] Significance of delayed primary excision in localized nonmetastatic adult head and neck rhabdomyosarcoma (2016)
  • Author(s): Kobayashi K, Matsumoto F, Kodaira M, Mori T, Murakami N, Yoshida A, Maki D, Teshima M, Fukasawa M, Itami J, Asai M, Yoshimoto S.
  • Journal Title: Cancer Med. Volume: 5 Issue: 10 Pages: 2708-2714
  • DOI: 10.1002/cam4.855
  • Peer Reviewed / Open Access
• [Presentation] Risk factors for delayed surgical recovery and massive bleeding in skull base surgery (2019)
  • Author(s): Kenya Kobayashi et al.
  • Organizer: 6th Congress of Asian Society of Head and Neck Oncology
  • Int'l Joint Research
• [Presentation] 当科における頭蓋底手術の切除および断端評価の工夫 (2019)
  • Author(s): 小林謙也 吉本世一 他
  • Organizer: 第29回頭頚部外科学会
• [Presentation] 1.Combined p53 analysis with gene sequencing and immunostaining for head and neck cancer. (2018)
  • Author(s): Kenya Kobayashi et al.
  • Organizer: the 119th annual meeting of the ORL Society Japan
• [Presentation] 2.Clinical impact of combined p53 analysis with gene sequencing and immunostaining for head and neck squamous cell carcinoma. (2018)
  • Author(s): Kenya Kobayashi et al.
  • Organizer: 17th Korea-Japan Joint Meeting ORL-HNS
  • Int'l Joint Research
• [Presentation] 予後不良なTP53ミスセンス変異の検討 (2018)
  • Author(s): 小林謙也 吉本世一 他
  • Organizer: 第42回頭頸部癌学会
• [Presentation] Impact of p53 status in surgical treatment of head and neck squamous cell carcinoma (2017)
  • Author(s): Kobayashi K, Mori T, Matsumoto F, Murakami N, Teshima M, Fukasawa M, Matsumoto Y, Matsumura S, Itami J, Asai M, Yoshimoto S.
  • Organizer: 5th congress of asian society of head and neck oncology
  • Place of Presentation: Bali
  • Year and Date: 2017-03-23
  • Int'l Joint Research
• [Presentation] 頭頸部扁平上皮癌の外科治療におけるp53免疫染色の意義 (2017)
  • Author(s): 小林 謙也、森 泰昌、松村 聡子、松本 吉史、深澤 雅彦、手島 直則、松本 文彦、吉本 世一
  • Organizer: 第27回日本頭頸部外科学会
  • Place of Presentation: 東京
  • Year and Date: 2017-02-02
• [Presentation] 免疫染色とシーケンスの併用による p53機能分類 (2017)
  • Author(s): 小林 謙也、森 泰昌、松村 聡子、松本 吉史、深澤 雅彦、手島 直則、松本 文彦、吉本 世一
  • Organizer: 日本頭頸部癌学会
• [Presentation] Impact of p53 status in surgical treatment of head and neck squamous cell carcinoma (2017)
  • Author(s): Kenya Kobayashi, Taisuke Mori, Fumihiko Matsumoto, Masanori Teshima, Masahiko Fukasawa, Yoshifumi Matsumoto, Satoko Matsumura, Seiichi Yoshimoto
  • Organizer: 5th Congress of Asian Society of Head and Neck Oncology
• [Presentation] 頭頸部扁平上皮癌の外科治療における p53免疫染色の意義 (2017)
  • Author(s): 小林 謙也、森 泰昌、松村 聡子、松本 吉史、深澤 雅彦、手島 直則、松本 文彦、吉本 世一
  • Organizer: 頭頸部外科学会
• [Presentation] Siginificance of surgery for head and neck sarcoma with skull base invasion (2016)
  • Author(s): Kenya Kobayashi, Yasuji Miyakita, Fumihiko Matsumoto, Makoto Kodaira, Taisuke Mori, Naoya Murakami, Daisuke Maki, Masanori Teshima, Masahiko Fukasawa, Yoshitaka Narita, Seiichi Yoshimoto
  • Organizer: 7th international congress of the World Federation of Skull Base Societies
  • Place of Presentation: Osaka
  • Year and Date: 2016-06-14
  • Int'l Joint Research
• [Presentation] 当院における頭蓋底浸潤を伴う肉腫の治療戦略 (2016)
  • Author(s): 小林謙也、宮北 康二、森 泰昌、吉田 明彦、下井 辰徳、松本 吉史、深澤 雅彦、手島 直則、松本 文彦、成田 善孝、吉本 世一
  • Organizer: 第４０回日本頭頚部癌学会
  • Place of Presentation: さいたま市
  • Year and Date: 2016-06-09