Identification and analyses of cancer stem-like cells in large cell neuroendocrine carcinoma of the lung

2013 Fiscal Year Final Research Report

• Project/Area Number: 24791481
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Thoracic surgery
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: HISHIDA Tomoyuki 独立行政法人国立がん研究センター, その他部局等, 研究員 (40544664)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 肺高悪性度神経内分泌癌 / がん幹細胞 / 小細胞癌 / 大細胞神経内分泌癌

Research Abstract

We evaluated the expression and clinical significance of cancer stem-like cells (CSLC) markers in high-grade neuroendocrine carcinoma (HGNEC) of the lung, comprising small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) in order to develop new treatment strategy. The expression of putative CSLC markers were examined immunohistochemically by using resected tumor specimens. HGNEC of the lung had various range of positive expression of CSLC markers. Among explored CSLC markers, ALDH1 expression was related to patient outcomes. ALDH1-positive HGNEC had significantly poorer survival than those with ALDH1- negative HGNEC. Multivariate analysis also revealed positive ALDH1 expression as an independent unfavorable prognostic factors. ALDH1-positive tumor cells were frequently observed even in micro lymph node metastases. These induced that targeting for ALDH1-positive tumor cells might be a future treatment strategy in HGNEC of the lung.

Research Products

• [Journal Article] Surgical outcomes after initial surgery for clinical single-station N2 non-small-cell lung cancer (2014)
  • Author(s): Hishida T, Yoshida J, Ohe Y, Aokage K, Ishii G, Nagai K
  • Journal Title: Jpn J Clin Oncol Volume: 44 Pages: 85-92
• [Journal Article] Identification of prognostic immunophenotypic features in cancer stromal cells of high-grade neuroendocrine carcinomas of the lung (2013)
  • Author(s): Takahashi A, Ishii G, Kinishita T, Yoshida T, Umemura S, Hishida T, Yoh K, Niho S, Goto K, Ohmatsu H, Ohe Y, Nagai K, Ochiai A
  • Journal Title: J Cancer Res Clin Oncol Volume: 139 Pages: 1869-78
• [Journal Article] Prognostic impact of intratumoural microvascular invasion and microlymphatic permeation on node-negative non-small-cell lung cancer : which indicator is the stronger prognostic factor? (2013)
  • Author(s): Hishida T, Yoshida J, Maeda R, Ishii G, Aokage K, Nishimura M, Nagai K
  • Journal Title: Eur J Cardiothorac Surg Volume: 43 Pages: 772-7
• [Journal Article] (2013)
  • Author(s): Hishida T, Yoshida J, Ishii G, Nagai K. Reply to Wang, et al
  • Journal Title: Eur J Cardiothorac Surg Volume: 43 Pages: 1270
• [Presentation] 大細胞神経内分泌癌の予後因子 混合型大細胞神経内分泌癌を中心として (2013)
  • Author(s): 三好智裕, 菱田智之, 石井源一郎, 仁保誠治, 荒牧直, 松村勇輝, 青景圭樹, 吉田純司, 大江裕一郎, 永井完治
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京
  • Year and Date: 20131100
• [Presentation] Extended bronchoplasty for locally advanced lung cancer to avoid pneumonectomy (2013)
  • Author(s): Hishida T
  • Organizer: 21th European Conference on General Thoracic Surgery
  • Place of Presentation: Birmingham, UK
  • Year and Date: 20130500
• [Presentation] Survival after bilateral lung resections of primary lung cancer with contralateral satellite nodules : should a small number of contralateral nodules be treated as M1a disease? (2012)
  • Author(s): Hishida T
  • Organizer: 20th European Conference on General Thoracic Surgery
  • Place of Presentation: Essen, Germany
  • Year and Date: 20120600