Lung cancer classification based on oncogene addiction

• Project/Area Number: 20390105
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: ISHIKAWA Yuichi Japanese Foundation For Cancer Research, 癌研究所病理部, 部長 (80222975)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 肺癌 / 遺伝子転座 / キナーゼ / 組織型 / EML4-ALK融合遺伝子 / EGFR変異

Research Abstract

We reported 5 lung cancer cases with EML4-ALK translocation in collaboration with Prof. H. Manu, Jichi Medical College, followed by identifying further 6 such cases. Interestingly, all these tumors were adenocarcinoma and lacked oncogene mutations of EGFR, K-ras and c-Met. This findings clearly indicated that ALK translocation was mutually exclusive from EGFR, K-RAS and c-MET mutations and strongly suggest that lung adenocarcinoma can be classified by oncogene changes.

Research Products

• [Journal Article] ASCL1-coexpression profiling but not single gene expression profiling defines lung adenocarcinomas of neuroendocrine nature with poor prognosis. (2011)
  • Author(s): Fujiwara T, Hiramatsu M, Isagawa T, Ninomiya H, Inamura K, Ishikawa S, Ushijima M, Matsuura M, Jones HM, Shimane M, Nomura H, Ishikawa Y, Aburatani Y
  • Journal Title: Lung Cancer (in press)
• [Journal Article] The impact of superior mediastinal lymph node metastases on prognosis in non-small cell lung cancer located in the right middle lobe. (2011)
  • Author(s): Sakao Y, Okumura S, Mun M-y, Uehara H, Ishikawa Y, Nakagawa K.
  • Journal Title: J Thorac Oncol 6(3) Pages: 494-9
• [Journal Article] Pulmonary inflammatory myofibroblastic tumor expressing a novel fusion, PPFIBP1-ALK : reappraisal of anti-ALK immunohisto- chemistry as a tool for novel ALK-fusion identification. (2011)
  • Author(s): Takeuchi K, Soda M, Togashi Y, Sugawara E, Hatano S, Asaka R, Okumura S, Nakagawa K, Mano H, Ishikawa Y
  • Journal Title: Clin Cancer Res. 17(10) Pages: 3341-8
• [Journal Article] International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. (2011)
  • Author(s): Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D.
  • Journal Title: J Thorac Oncol. 6(2) Pages: 244-85
• [Journal Article] Clinicopathological findings of non-small-cell lung cancer with high serum progastrin-releasing peptide concentrations. (2011)
  • Author(s): Kudo K, Ohyanagi F, Horiike A, Miyauchi E, Yanagitani N, Hoshi R, Satoh Y, Motoi N, Hamanaka W, Ishikawa Y, Mun M, Sakao Y, Okumura S, Nakagawa K, Horai T, Nishio M.
  • Journal Title: Lung Cancer. (Epub ahead of print)
• [Journal Article] 肺野に孤立性陰影を認めた悪性胸膜中皮腫の1例 (2011)
  • Author(s): 宮内栄作,工藤慶太,星利良,古田則行,平井康夫,元井紀子,石川雄一,宝来威
  • Journal Title: 日本臨床細胞学会雑誌 50(2) Pages: 115-9
  • NAID: 10027955567
• [Journal Article] トランスクリプトームによる病態解析.第3部 病理組織検体を用いたオーム研究:疾患関連分子同定への挑戦. (2011)
  • Author(s): 稲村健太郎、元井紀子、石川雄一
  • Journal Title: 病理と臨床 29:臨時増刊号 Pages: 522-528
• [Journal Article] 検診を契機に診断した気管支顆粒細胞腫の1例 (2011)
  • Author(s): 田中寿志,工藤慶太,文敏景,元井紀子,石川雄一,宝来威.
  • Journal Title: 日呼吸会誌 49(2) Pages: 128-130
  • NAID: 10029087523
• [Journal Article] Bone metastasis and poor performance status are prognostic factors for survival of carcinoma of unknown primary site in patients treated with systematic chemotherapy. (2010)
  • Author(s): Kodaira M, Takahashi S, Yamada S, Ueda K, Mishima Y, Takeuchi K, Yamamoto N, Ishikawa Y, Yokoyama M, Saotome T, Terui Y, Hatake K
  • Journal Title: Ann Oncol.(Epub 2009 Dec 17.) 21(6) Pages: 1163-7
• [Journal Article] Role of insulin-like growth factor binding proteins 2 in lung cancer : IGF independent anti-apoptotic effect via caspase-3. (2010)
  • Author(s): Migita T, Narita T, Asaka R, Miyagi E, Nagano H, Nomura K, Matsuura M, Satoh Y, Okumura S, Nakagawa K, Seimiya H, Ishikawa Y
  • Journal Title: Am J Pathol 176 Pages: 1756-66
• [Journal Article] Activation status of receptor tyrosine kinase downstream pathways in primary lung adenocarcinoma with reference of KRAS and EGFR mutations. (2010)
  • Author(s): Hiramatsu M, Ninomiya H, Inamura K, Nomura K, Takeuchi K, Satoh Y, Okumura S, Nakagawa K, Yamori T, Matsuura M, Morikawa T, Ishikawa Y
  • Journal Title: Lung Cancer 70 Pages: 94-102
• [Journal Article] Is the epidermal growth factor receptor status in lung cancers reflected in clinicopathologic features? (2010)
  • Author(s): Inamura K, Ninomiya H, Ishikawa Y, Matsubara O.
  • Journal Title: Arch Pathol Lab Med. 134(1) Pages: 66-72
• [Journal Article] Primary pulmonary meningioma : Ten-year follow-up findings for a multiple case, implying a benign biological nature. (2010)
  • Author(s): Satoh Y, Ishikawa Y
  • Journal Title: J Thorac Cardiovasc Surg. e39-40
• [Journal Article] Discriminant model for cytologic distinction of large cell neuroendocrine carcinoma from small cell carcinoma of the lung. (2010)
  • Author(s): Hoshi R, Furuta N, Horai T, Ishikawa Y, Miyata S, Satoh Y
  • Journal Title: J Thorac Oncol. (4);5 Pages: 472-8
• [Journal Article] Implications for differential diagnosis of lung cancer-associated lymphadenopathy in lymphoepithelioid cell lymphoma (Lennert's lymphoma) arising simul- taneously with lung cancer : a case report. (2010)
  • Author(s): Hoshi R, Furuta N, Horai T, Takeuchi K, Ishikawa Y, Satoh Y
  • Journal Title: Acta Cytol. 54(2) Pages: 197-201
• [Journal Article] Function of EWS-POU5F1 in sarcomagenesis and tumor cell maintenance. (2010)
  • Author(s): Fujino T, Nomura K, Ishikawa Y, Makino H, Umezawa A, Aburatani H, Nagasaki K, Nakamura T.
  • Journal Title: Am J Pathol. 176(4) Pages: 1973-82
• [Journal Article] Lung cancer progression and metastasis from the prognostic point of view. (2010)
  • Author(s): Inamura K, Ishikawa Y
  • Journal Title: Clin Exp Metastasis. 27 Pages: 389-97
• [Journal Article] Prognostic heterogeneity in multilevel N2 non-small cell lung cancer patients : importance of lymphadenopathy and occult intra- pulmonary metastases. (2010)
  • Author(s): Sakao Y, Okumura S, Mun M, Uehara H, Ishikawa Y, Nakagawa K
  • Journal Title: Ann Thorac Surg. 89(4) Pages: 1060-3
• [Journal Article] Predictive advantage of a cell type classification for pulmonary adenocarcinoma coupled with data for p53, K-ras and EGFR alterations. (2010)
  • Author(s): Okada A, Shimmyo T, Hashimoto T, Kobayashi Y, Miyagi Y, Ishikawa Y, Nakagawa K, Hayashi J, Tsuchiya E
  • Journal Title: Cancer Sci.(Epub 2010 Apr 7) 101(7) Pages: 1745-53
  • NAID: 10026595179
• [Journal Article] Surgical resection for oral tongue cancer pulmonary metastases. (2010)
  • Author(s): Mochizuki T, Okumura S, Ishii G, Ishikawa Y, Hayashi R, Kawabata K, Yoshida J
  • Journal Title: Interact Cardiovasc Thorac Surg.(Epub 2010 Mar 31) 11(1) Pages: 56-9
• [Journal Article] Dlk-1, a cell surface antigen on foetal hepatic stem/progenitor cells, is expressed in hepatocellular, colon, pancreas and breast carcinomas at a high frequency. (2010)
  • Author(s): Yanai H, Nakamura K, Hijioka S, Kamei A, Ikari T, Ishikawa Y, Shinozaki E, Mizunuma N, Hatake K, Miyajima A.
  • Journal Title: J Biochem.(Epub 2010 Mar 30) 148(1) Pages: 85-92
  • NAID: 10027877210
• [Journal Article] Cytokeratin expression profiling is useful for distinguishing between primary squamous cell carcinoma of the lung and pulmonary metastases from tongue cancer. (2010)
  • Author(s): Ohba T, Motoi N, Kimura Y, Okumura S, Kawabata K, Yoshizawa Y, Inase N, Ishikawa Y
  • Journal Title: Pathol Int. 60(8) Pages: 575-80
  • NAID: 10030721097
• [Journal Article] Correlating phosphatidylinositol 3- kinase inhibitor efficacy with signaling pathway status: in silico and biological evaluations. (2010)
  • Author(s): Dan S, Okamura M, Seki M, Yamazaki K, Sugita H, Okui M, Mukai Y, Nishimura H, Asaka R, Nomura K, Ishikawa Y, Yamori T
  • Journal Title: Cancer Res.(Epub 2010 Jun 8.) 70(12) Pages: 4982-94
• [Journal Article] Feasibility of antegrade radical prostatectomy for clinically locally advanced prostate cancer : a comparative study with clinically localized disease. (2010)
  • Author(s): Yamamoto S, Kawakami S, Yonese J, Fujii Y, Tsukamoto T, Okubo Y, Kijima T, Ishikawa Y, Fukui I
  • Journal Title: Int J Urol. 17(8) Pages: 720-5
  • NAID: 10027259627
• [Journal Article] Prognostic value and significance of subcarinal and superior mediastinal lymph node metastasis in lower lobe tumours. (2010)
  • Author(s): Uehara H, Sakao Y, Mun M, Nakagawa K, Nishio M, Ishikawa Y, Okumura S
  • Journal Title: Eur J Cardiothorac Surg. 38 Pages: 498-502
• [Journal Article] Dedifferentiated liposarcoma with rhabdomyoblastic differentiation in an 8-year-old girl. (2010)
  • Author(s): Okamoto S, Machinami R, Tanizawa T, Matsumoto S, Lee GH, Ishikawa Y
  • Journal Title: Pathol Res Pract. 206(3) Pages: 191-196
• [Journal Article] Intrinsic co- operation between p16INK4a and p21Waf1/ Cip1 in the onset of cellular senescence and tumor suppression in vivo. (2010)
  • Author(s): Takeuchi S, Takahashi A, Motoi N, Yoshimoto S, Tajima T, Yamakoshi K, Hirao A, Yanagi S, Fukami K, Ishikawa Y, Sone S, Hara E, Ohtani N
  • Journal Title: Cancer Res. 70(22) Pages: 9381-90
• [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. 363(18) Pages: 1734-9
• [Journal Article] Cancer of unknown primary site : a review of 28 cases and the efficacy of cisplatin/docetaxel therapy at a single institute in Japan. (2010)
  • Author(s): Nishimori H, Takahashi S, Kiura K, Ennishi D, Kobayashi T, Sano K, Shinozaki E, Yokoyama M, Mishima Y, Terui Y, Chin K, Mizunuma N, Ito Y, Nishimura S, Takeuchi K, Ishikawa Y, Oguchi M, Tanimoto M, Hatake K
  • Journal Title: Acta Med Okayama. 64(5) Pages: 285-91
• [Journal Article] ラブドイド細胞が目立った肺大細胞神経内分泌癌の1例 (2010)
  • Author(s): 鈴木奈緒子,星利良,佐藤之俊,古田則行,宮内栄作,石川雄一,平井康夫,宝来威
  • Journal Title: 日本臨床細胞学会雑誌 49 Pages: 15-19
  • NAID: 10025946843
• [Journal Article] 肺がんの分類-癌遺伝子による分類の可能性 (2010)
  • Author(s): 石川雄一
  • Journal Title: 喫煙科学 24(4) Pages: 4-4
• [Journal Article] 肺神経内分泌腫瘍の分類と組織診断 (2010)
  • Author(s): 大場岳彦,石川雄一
  • Journal Title: 病理と臨床 28(2) Pages: 151-155
• [Journal Article] 微小乳頭状腺癌・腸型腺癌 (2010)
  • Author(s): 二宮浩範,石川雄一
  • Journal Title: 病理と臨床 28(3) Pages: 259-262
• [Journal Article] 神経内分泌形態,第3章肺-腫瘍- (2010)
  • Author(s): 苅田真,石川雄一
  • Journal Title: 病理形態学キーワード(文光堂)(臨時増刊号,病理と臨床) vol.28
• [Journal Article] ALK肺癌の臨床病理学的特徴-形態からわかるその疫学的背景 (2010)
  • Author(s): 石川雄一
  • Journal Title: 呼吸器内科 18(4) Pages: 362-367
• [Journal Article] Intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in theonset of cellular senescence and tumor suppression in vivo. (2010)
  • Author(s): Takeuchi S, et al.
  • Journal Title: Cancer Res. Volume: 70 Pages: 9381-9390
  • Peer Reviewed
• [Journal Article] ALK Lung Cancer Study Group.EML4-ALK mutations in lung cancerthat confer resistance to ALK inhibitors (2010)
  • Author(s): Choi YL, et al.
  • Journal Title: N Engl J Med. Volume: 363 Pages: 1734-1739
  • Peer Reviewed
• [Journal Article] Role of insulin-like growth factor binding proteins 2 in lung cancer : IGF independent anti-apoptotic effect via caspase-3 (2010)
  • Author(s): Migita T, et al.
  • Journal Title: Am J Pathol Volume: 176 Pages: 1756-1766
  • Peer Reviewed
• [Journal Article] Adult Xp11 translocation renal cell carcinoma diagnosed by cytogenetics and immunohistochemistry. (2009)
  • Author(s): Komai Y, Fujiwara M, Fujii Y, Mukai H, Yonese J, Kawakami S, Yamamoto S, Migita T, Ishikawa Y, Kurata M, Nakamura T, Fukui I
  • Journal Title: Clin Cancer Res 15(4) Pages: 1170-6
• [Journal Article] Correlation between morphology and EGFR mutations in lung adenocarcinomas. Significance of the micropapillary pattern and the hobnail cell type. (2009)
  • Author(s): Ninomiya H, Hiramatsu M, Inamura K, Nomura K, Okui M, Miyoshi T, Okumura S, Satoh Y, Nakagawa K, Nishio M, Horai T, Miyata S, Tsuchiya E, Fukayama M, Ishikawa Y
  • Journal Title: Lung Cancer 63(2) Pages: 235-40
• [Journal Article] KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. (2009)
  • Author(s): Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, Takada S, Ueno T, Yamashita Y, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y, Mano H
  • Journal Title: Clin Cancer Res 15(9) Pages: 3143-9
• [Journal Article] EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. (2009)
  • Author(s): Inamura K, Takeuchi K, Togashi Y, Hatano S, Ninomiya H, Motoi N, Mun MY, Sakao Y, Okumura S, Nakagawa K, Soda M, Lim Choi Y, Mano H, Ishikawa Y
  • Journal Title: Mod Pathol. 22 Pages: 508-515
• [Journal Article] Frequent inactivation of A20 in B-cell lymphomas. (2009)
  • Author(s): Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Muto S, Tamura A, Iio M, Akatsuka Y, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, Tobinai K, Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S.
  • Journal Title: Nature 459 Pages: 712-6
• [Journal Article] Risk stratification of high-grade prostate cancer treated with antegrade radical prostatectomy with intended wide resection. (2009)
  • Author(s): Yamamoto S, Kawakami S, Yonese J, Fujii Y, Tsukamoto T, Ohkubo Y, Komai Y, Ishikawa Y, Fukui I
  • Journal Title: Jpn J Clin Oncol 39(6) Pages: 387-93
• [Journal Article] Kruppel-like factor 12 plays a significant role in poorly differentiated gastric cancer progression. (2009)
  • Author(s): Nakamura Y, Migita M, Hosoda F, Okada N, Gotoh M, Arai Y, Fukushima M, Ohki M, Miyata S, Takeuchi K, Imoto I, Katai H, Yamaguchi T, Inazawa J, Hirohashi S, Ishikawa Y, Shibata T
  • Journal Title: Int J Cancer 125 Pages: 1859-67
• [Journal Article] Mesenchymal to embryonic incomplete transition of human cells by chimeric OCT4/3 (POU5F1) with physiological co-activator EWS. (2009)
  • Author(s): Makino H, Toyoda M, Matsumoto K, Saito H, Nishino K, Fukawatase Y, Machida M, Akutsu H, Uyama T, Miyagawa Y, Okita H, Kiyokawa N, Fujino T, Ishikawa Y, Nakamura T, Umezawa A
  • Journal Title: Exp Cell Res. 315(16) Pages: 2727-40
• [Journal Article] Association of cytologic micropapillary clusters in cytology samples with lymphatic spread in clinical stage I lung adenocarcinomas. (2009)
  • Author(s): Satoh Y, Hoshi R, Horai T, Okumura S, Nakagawa K, Ishikawa Y, Miyata S
  • Journal Title: Lung Cancer 64(3) Pages: 277-81
• [Journal Article] Functional in vivo optical imaging of tumor angiogenesis, growth, and metastasis prevented by administration of anti-human VEGF antibody in xenograft model of human fibrosarcoma HT1080 cells. (2009)
  • Author(s): Hanyu A, Kojima K, Hatake K, Nomura K, Murayama H, Ishikawa Y, Miyata S, Ushijima M, Matsuura M, Ogata E, Miyazawa K, Imamura T
  • Journal Title: Cancer Sci. 100 Pages: 2085-92
  • NAID: 10027196865
• [Journal Article] 肺の神経内分泌性腫瘍の病理学,特に大細胞神経内分泌癌について (2009)
  • Author(s): 中村裕,石川雄一
  • Journal Title: 呼吸 28 Pages: 33-6
• [Journal Article] Correlation between morphology and EGFR mutations in lung adenocarcinomas (2009)
  • Author(s): Ninomiya H, et al.
  • Journal Title: Lung Cancer 63 Pages: 235-240
  • Peer Reviewed
• [Journal Article] KIF5B-ALK, a novel fusion oncokinase identified by an immuno histochemistry-based diagnostic system for ALK-positive lung cancer (2009)
  • Author(s): Takeuchi K, et al.
  • Journal Title: Clin Cancer Res 15 Pages: 3143-3149
  • Peer Reviewed
• [Journal Article] EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset (2009)
  • Author(s): Inamura, et al.
  • Journal Title: Mod Pathol 22 Pages: 508-515
  • Peer Reviewed
• [Journal Article] Multiplex RT-PCR screening for EML4-ALK fusion transcripts (2008)
  • Author(s): Takeuchi K, Ishikawa Y, et al.
  • Journal Title: Clin Cancer Res 14(20) Pages: 6618-6624
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers (2008)
  • Author(s): Inamura K, Ishikawa Y, et al.
  • Journal Title: J Thorac Oncol 3(1) Pages: 13-17
  • Peer Reviewed
• [Journal Article] Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer (2008)
  • Author(s): Choi YL, Ishikawa Y, et al.
  • Journal Title: Cancer Res 68(13) Pages: 4971-4976
  • Peer Reviewed
• [Presentation] 教育講演III肺癌「肺癌の病理診断における最近のトピック」 (2010)
  • Author(s): 石川雄一
  • Organizer: 日本臨床細胞学会関東連合学術集会
  • Place of Presentation: 軽井沢
  • Year and Date: 2010-09-18
• [Presentation] New aspects of pathological diagnosis and classification of cancer : focusing on miRNA expression and signaling pathways. (2010)
  • Author(s): 石川雄一
  • Organizer: Symposium 5 "Advancement of cancer pathology diagnosis and its future development" Jpn Cancer Assoc 69th Annual Meeting
  • Place of Presentation: Osaka
• [Presentation] New aspects of pathological diagnosis and classification of cancer : focusing on miRNA expression and signaling pathways. (2010)
  • Author(s): Ishikawa Y.
  • Organizer: Jpn Cancer Assoc 69th Annual Meeting
  • Place of Presentation: 大阪
• [Presentation] Multiple Tumor Nodules : characteristics of lung cancers with multiple nodules from BAC to ALK fusion gene carcinoma (2009)
  • Author(s): Ishikawa, Y.
  • Organizer: 13-th World Congress of Lung Cancer, IASLC
  • Place of Presentation: San Francisco, USA
• [Book] 神経内分泌形態(病理形態学キーワード(第3章 肺-腫瘍-)) (2010)
  • Author(s): 苅田真,石川雄一(分担執筆)
  • Publisher: 文光堂
• [Book] 病理形態学キーワード(神経内分泌形態) 第3章 肺-腫瘍- (2010)
  • Author(s): 苅田真, 石川雄一(分担執筆)
  • Total Pages: 446
  • Publisher: 文光堂
• [Remarks] ホームページ等