Analysis of lung adenocarcinoma according to molecular biological classification

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390110
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: YATABE Yasushi 愛知県がんセンター(研究所), 分子腫瘍学部, 研究員 (90280809)
• Co-Investigator(Kenkyū-buntansha): MITSUDOMI Tetsuya 愛知県がんセンター研究所, 分子腫瘍学部, 研究員 (70209807)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Takashi 名古屋大学, 大学院・医学研究科, 教授 (50231395)
• Project Period (FY): 2009 – 2011
• Keywords: 呼吸器 / 縦隔(肺腺癌、分子病理学)

Research Abstract

We carried out this study according to four themes that we initially laid out. For analysis of preinvasive and in-situ lesions, we could establish definition of adenocarcinoma in-situ in the new adenocarcinoma classification as a member of the IASLC pathology panel. We are still analyzing multiple lesions using SNP array that is of our second theme. To the third theme of intra-tumor heterogeneity, we could show that different EGFR mutation status within individual tumors was caused by combination of heterogeneous distribution of gene amplification and mutation allele specific imbalance, and we called the phenomenon"pseudo-heterogeneity". We have also achieved sufficient results for the fourth theme, because we participated in international collaborative studies to establish ALK diagnostic algorithm and established it as a guidance requested from the Japanese Lung Cancer Association.

Research Products

• [Journal Article] Do All Lung Adenocarcinomas Follow a Stepwise Progression? (2011)
  • Author(s): Yatabe Y, Borczuk AC, Powell CA
  • Journal Title: Lung Cancer Volume: 74 Pages: 7-11
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y
  • Journal Title: J Thorac Oncol Volume: 6 Pages: 244-85
  • Peer Reviewed
• [Journal Article] Role and Relevance of Trkb Mutations and Expression in Non-Small Cell Lung Cancer (2011)
  • Author(s): Harada T, Yatabe Y, Takeshita M, Koga T, Yano T, Wang Y, Giaccone G.
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 2638-45
  • Peer Reviewed
• [Journal Article] Heterogeneous Distribution of EGFR Mutations Is Extremely Rare in Lung Adenocarcinoma (2011)
  • Author(s): Yatabe Y, Matsuo K, Mitsudomi T
  • Journal Title: J Clin Oncol Volume: 29 Pages: 2972-7
  • Peer Reviewed
• [Journal Article] ALK Lung Cancer Study Group. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors (2010)
  • Author(s): Choi YL, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H
  • Journal Title: N Engl J Med Volume: 363 Pages: 1734-9
  • Peer Reviewed
• [Journal Article] Clinically Relevant Characterization of Lung Adenocarcinoma Subtypes Based on Cellular Pathways (2010)
  • Author(s): Bryant CM, Albertus DL, Kim S, Chen G, Brambilla C, Guedj M, Arima C, Travis WD, Yatabe Y
  • Journal Title: PLoS One Volume: 5 Pages: e11712
  • Peer Reviewed
• [Journal Article] Thyroid Transcription Factor 1 Expression in Ovarian Carcinomas Is an Independent Prognostic Factor (2010)
  • Author(s): Fujiwara S, Nawa A, Yatabe Y
  • Journal Title: Hum Pathol Volume: 41 Pages: 560-5
  • Peer Reviewed
• [Journal Article] Analysis of Genetic Variants in Never-Smokers with Lung Cancer Facilitated by an Internet-Based Blood Collection Protocol (2010)
  • Author(s): Girard N, Lou E, Azzoli CG, Reddy R, Robson M, Harlan M, Orlow I, Yatabe Y
  • Journal Title: A Preliminary Report. Clin Cancer Res Volume: 16 Pages: 755-63
  • Peer Reviewed
• [Journal Article] Regulation of DNA Polymerase Pold4 Influences Genomic Instability in Lung Cancer (2010)
  • Author(s): Huang QM, Tomida S, Masuda Y, Arima C, Cao K, Kasahara TA, Osada H, Yatabe Y, Akashi T, Kamiya K, Takahashi T, Suzuki M.
  • Journal Title: Cancer Res Volume: 70 Pages: 8407-16
  • Peer Reviewed
• [Journal Article] Immunohistochemical Detection of Egfr Mutation Using Mutation-Specific Antibodies in Lung Cancer (2010)
  • Author(s): Kitamura A, Hosoda W, Sasaki E, Mitsudomi T, Yatabe Y.
  • Journal Title: Clin Cancer Res Volume: 16 Pages: 3349-55
  • Peer Reviewed
• [Journal Article] Egfr Mutations and the Terminal Respiratory Unit (2010)
  • Author(s): Yatabe Y.
  • Journal Title: Cancer Metastasis Rev Volume: 29 Pages: 23-36
  • Peer Reviewed
• [Journal Article] Pathologic Diagnosis of Advanced Lung Cancer Based on Small Biopsies and Cytology (2010)
  • Author(s): Travis WD, Rekhtman N, Riley GJ, Geisinger KR, Asamura H, Brambilla E, Garg K, Hirsch FR, Noguchi M, Powell CA, Rusch VW, Scagliotti G, Yatabe Y.
  • Journal Title: J Thorac Oncol Volume: 5 Pages: 411-4
  • Peer Reviewed
• [Journal Article] Gefitinib Versus Cisplatin Plus Docetaxel in Patients with Non-Small-Cell Lung Cancer Harbouring Mutations of the Epidermal Growth Factor Receptor(Wjtog3405) (2010)
  • Author(s): Mitsudomi T, Morita S, Yatabe Y, et al
  • Journal Title: An Open Label, Randomised Phase 3 Trial Volume: 11 Pages: 121-8
  • Peer Reviewed
• [Journal Article] Reciprocal and Complementary Role of Met Amplification and Egfr T790m Mutation in Acquired Resistance to Kinase Inhibitors in Lung Cancer (2010)
  • Author(s): Suda K, Murakami I, Katayama T, Tomizawa K, Osada H, Sekido Y, Maehara Y, Yatabe Y, Mitsudomi T
  • Journal Title: Clin Cancer Res Volume: 16 Pages: 5489-98
  • Peer Reviewed
• [Journal Article] Epidermal growth factor receptor in relation to tumor development (2010)
  • Author(s): Mitsudomi T, Yatabe Y.
  • Journal Title: EGFR gene and cancer Volume: 277(2) Pages: 301-8
  • Peer Reviewed
• [Journal Article] Relationship of Deregulated Signaling Converging onto Mtor with Prognosis and Classification of Lung Adenocarcinoma Shown by Two Independent in Silico Analyses (2009)
  • Author(s): Ebi H, Tomida S, Takeuchi T, Arima C, Sato T, Mitsudomi T, Yatabe Y, Osada H, Takahashi T
  • Journal Title: Cancer Res Volume: 69 Pages: 4027-35
  • Peer Reviewed
• [Journal Article] Combined Inhibition of Met and Egfr Suppresses Proliferation of Malignant Mesothelioma Cells (2009)
  • Author(s): Kawaguchi K, Murakami H, Taniguchi T, Fujii M, Kawata S, Fukui T, Kondo Y, Osada H, Usami N, Yokoi K, Ueda Y, Yatabe Y, Ito M, Horio Y, Hida T, Sekido Y.
  • Journal Title: Carcinogenesis
  • Peer Reviewed
• [Journal Article] Prognostic Implication of Egfr, Kras, and Tp53 Gene Mutations in a Large Cohort of Japanese Patients with Surgically Treated Lung Adenocarcinoma (2009)
  • Author(s): Kosaka T, Yatabe Y, Onozato R, Kuwano H, Mitsudomi T.
  • Journal Title: J Thorac Oncol Volume: 4 Pages: 22-9
  • Peer Reviewed
• [Journal Article] Relapse-Related Molecular Signature in Lung Adenocarcinomas Identifies Patients with Dismal Prognosis (2009)
  • Author(s): Tomida S, Takeuchi T, Shimada Y, Arima C, Matsuo K, Mitsudomi T, Yatabe Y, Takahashi T.
  • Journal Title: J Clin Oncol Volume: 27 Pages: 2793-9
  • Peer Reviewed
• [Journal Article] Egfr and Her2 Genomic Gain in Recurrent Non-Small Cell Lung Cancer after Surgery : Impact on Outcome to Treatment with Gefitinib and Association with Egfr and Kras Mutations in a Japanese Cohort (2009)
  • Author(s): Varella-Garcia M, Mitsudomi T, Yatabe Y, Kosaka T, Nakajima E, Xavier AC, Skokan M, Zeng C, Franklin WA, Bunn PA, Jr., Hirsch FR
  • Journal Title: J Thorac Oncol. Volume: 4 Pages: 318-25
  • Peer Reviewed
• [Journal Article] Mir-375 Is Activated by Ash1 and Inhibits Yap1 in a Lineage Dependent Manner in Lung Cancer
  • Author(s): Nishikawa E, Yatabe Y
  • Journal Title: Cancer Res Volume: (in press)
  • Peer Reviewed
• [Presentation] Is the EGFR mutation distributed heterogeneously within tumor? (2011)
  • Author(s): Yasushi YATABE
  • Organizer: The 100th annual meeting of US-Canadian Academy of Pathology
  • Place of Presentation: 米国・サンアントニオ
  • Year and Date: 20110000
• [Presentation] Is the EGFR Mutation Distributed Heterogeneously within Tumors? (2011)
  • Author(s): Yasushi YATABE
  • Organizer: Annual meeting of US-Canada Academy of Pathology, workshop
  • Place of Presentation: 米国・サンアントニオ
  • Year and Date: 20110000
• [Presentation] Diagnostic algorithm of ALK fusion ADC in clinical practice (2011)
  • Author(s): Yasushi YATABE
  • Organizer: 5th IASLC/ASCO/ESMO International Conference on Molecular Targeted Therapy in Lung Cancer at Malta
  • Place of Presentation: マルタ
  • Year and Date: 20110000
• [Presentation] Role of TTF-1 and EGFR Developmental Pathways In Lung Adenocarcinoma (2011)
  • Author(s): Yasushi YATABE
  • Organizer: Educational Symposium
  • Place of Presentation: 米国・コロラド
  • Year and Date: 20110000
• [Presentation] Pitfalls for EGFR mutation specific antibodies, oral workshop Molecular classification of lung carcinoma(1): Adenocarcinoma, oral workshop Standardization of IHC for ALK (2011)
  • Author(s): Yasushi YATABE
  • Organizer: Oral workshop IASLC Path Panel in fall workshop
  • Place of Presentation: つくば
  • Year and Date: 20110000
• [Presentation] Molecular correlation and classification of lung cancer (2011)
  • Author(s): Yatabe Y, Wistuba I
  • Organizer: IASLC Pathology Panel Meeting
  • Place of Presentation: つくば
  • Year and Date: 20110000
• [Presentation] Unveiling the Molecular Landscape of Lung Adenocarcinoma Development (2010)
  • Author(s): Yatabe Y
  • Organizer: The 4th Asia Pacific Lung Cancer Conference
  • Place of Presentation: 韓国・ソウル
  • Year and Date: 20101200
• [Presentation] EGFR mutation in lung cancer cell differentiation and survival (2010)
  • Author(s): Yatabe Y
  • Organizer: American Thoracic Society
  • Place of Presentation: 米国・ニューオリンズ
  • Year and Date: 20100500
• [Presentation] Morphological and Biological Characteristics of Lung Adenocarcinomas Harboring EGFR, KRAS, BRAF, HER2, and EML4-ALK Gene Alterations (2009)
  • Author(s): Yatabe Y
  • Organizer: The 49th Annual Meeting of the Japanese Respiratory Society
  • Place of Presentation: 東京
  • Year and Date: 20090000
• [Presentation] MEET THE EXPERT, An Emerging Concept of Lung Adenocarcinoma : What can we learn from EGFR, KRAS, BRAF, HER2 and EML4-ALK gene alterations? (2009)
  • Author(s): Yatabe Y
  • Organizer: The 13th World Conference on Lung Cancer
  • Place of Presentation: 米国・サンフランシスコ
  • Year and Date: 20090000
• [Presentation] TF-1 Positive Metastatic Cervical Cancer (2009)
  • Author(s): Yatabe Y
  • Organizer: The Third Korean-Japanese Joint Slide Conference of Lung Pathology
  • Place of Presentation: 名古屋
  • Year and Date: 20090000