Prediction of postoperative recurrences by gene expression profiling in patients with primary resected lung cancer

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591822
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kitasato University
• Principal Investigator: IYODA Akira 北里大学, 医学部, 准教授 (10302548)
• Co-Investigator(Kenkyū-buntansha): SATOH Yukitoshi 北里大学, 医学部, 教授 (90321637) ; AMANO Hideki 北里大学, 医学部, 助教 (60296481)
• Project Period (FY): 2009 – 2011
• Keywords: 肺癌 / テーラーメイド治療 / 予後 / 組織型

Research Abstract

We analyzed LCNEC gene expression, gene mutation and immunohistochemical expression of known molecular targets and compared expression to that of lung adenocarcinomas. We analyzed 13 patients with primary LCNEC and 14 patients with adenocarcinoma(AC). We evaluated immunohistochemical(IHC) expression for c-KIT, human epidermal growth factor receptor type 2(HER2), and vascular endothelial growth factor(VEGF), gene mutation for EGFR, K-ras and c-kit, and gene expression using fluorescence in situ hybridization(FISH) for EGFR. In cases with LCNEC, the IHC expression of c-KIT, HER2, and VEGF were 76.9%, 30.8%, and 100%, respectively. There was a significant difference in IHC expression in c-KIT and HER2 between LCNEC and AC. Two cases of LCNEC had overexpression of HER2, and EGFR gene mutation was greater in the AC group, with only a single EGFR mutation(exon 18) identified in the LCNEC group. Although LCNEC had a higher rate of expression of c-KIT by IHC, no c-kit gene mutations were found. These findings suggest a potential role for Anti-VEGF, Anti-c-KIT, and possibly Anti-HER2 targeted agents in the treatment of LCNEC.

Research Products

• [Journal Article] Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma (2011)
  • Author(s): Iyoda A, Travis WD, Sarkaria IS, Jiang SX, Amano H, Sato Y, Saegusa M, Rusch VW, Satoh Y
  • Journal Title: Exp Therap Med Volume: 2 Pages: 1041-1045
• [Journal Article] Prediction of postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease (2011)
  • Author(s): Iyoda A, Jiang SX, Amano H, Ogawa F, Matsui Y, Kurouzu N, Hara H, Nezu K, Mikami T, Saegusa M, Satoh Y
  • Journal Title: Exp Therap Med Volume: 2 Pages: 1073-1076
• [Journal Article] The current status and future direction of surgical treatments for lung cancer (2010)
  • Author(s): Rusch VW, 伊豫田明, 吉村博邦, 佐藤之俊, 早川和重
  • Journal Title: 肺癌 Volume: 50 Pages: 253-264
• [Journal Article] Predictors of postoperative survival in patients with locally advanced non-small cell lung carcinoma (2010)
  • Author(s): Iyoda A, Hiroshima K, Moriya Y, Yoshida S, Suzuki M, Shibuya K, Yoshino I
  • Journal Title: Surgery Today Volume: 40 Pages: 725-728
• [Presentation] 肺大細胞神経内分泌癌に対する遺伝子変異、蛋白発現解析 (2011)
  • Author(s): 伊豫田明、蒋世旭、根津賢司、小川史洋、松井啓夫、天野英樹、原英則、久朗津尚美、益田典幸、早川和重、佐藤之俊
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 誌上発表(予定東京)
  • Year and Date: 20110526-28
• [Presentation] 肺神経内分泌腫瘍に対する手術および術後補助療法に関する検討 (2011)
  • Author(s): 伊豫田明、蒋世旭、山崎宏継、石井大、中島裕康、小川史洋、松井啓夫、塩見和、原英則、久朗津尚美、益田典幸、早川和重、佐藤之俊
  • Organizer: 第52回日本肺癌学会総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2011-11-03
• [Presentation] 肺大細胞神経内分泌癌に対する分子標的治療を目的とした遺伝子変異、蛋白発現解析 (2010)
  • Author(s): 伊豫田明、蒋世旭、根津賢司、小川史洋、松井啓夫、天野英樹、原英則、久朗津尚美、益田典幸、早川和重、佐藤之俊
  • Organizer: 第51回日本肺癌学会総会・ワークショップ
  • Place of Presentation: 広島国際会議場(広島県)
  • Year and Date: 2010-11-04
• [Presentation] 肺大細胞神経内分泌癌切除症例における術後再発の検討 (2010)
  • Author(s): 伊豫田明、小川史洋、松井啓夫、天野英樹、久朗津尚美、原英則、根津賢司、吉村博邦、佐藤之俊
  • Organizer: 第63回日本胸部外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-10-27
• [Presentation] 間質性肺炎合併肺癌における術後急性増悪関連因子の検討 (2010)
  • Author(s): 伊豫田明、秋山啓輔、小川史洋、伊藤諭子、松井啓夫、天野英樹、原英則、根津賢司、吉村博邦、佐藤之俊
  • Organizer: 第27回日本呼吸器外科学会総会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 2010-05-13
• [Presentation] 肺癌治療のスタンダード-外科治療と補助療法との組み合わせ-肺大細胞神経内分泌癌の治療経験から (2010)
  • Author(s): 伊豫田明、蒋世旭、根津賢司、小川史洋、松井啓夫、天野英樹、原英則、岡安勲、益田典幸、早川和重、吉村博邦、佐藤之俊
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2010-04-10
• [Presentation] Postoperative recurrence and the prognosis in patients with pulmonary large cell neuroendocrine carcinoma (2009)
  • Author(s): Iyoda A, Jiang SX, Ijima D, Nezu K, Ogawa F, Matsui Y, Amano H, Hara H, Okayasu I, Masuda N, Hayakawa K, Yoshimura H, Satoh Y
  • Organizer: 13th World Conference on Lung Cancer
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2009-08-02