Establishment of a novel morphologic and genetic classification of brain tumors for aiming at better diagnosis that corresponds to the biologic activity of tumors.

2010 Fiscal Year Final Research Report

• Project/Area Number: 19300123
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Gunma University
• Principal Investigator: NAKAZATO Yoichi Gunma University, 大学院・医学系研究科, 教授 (10106908)
• Co-Investigator(Kenkyū-buntansha): HIRATO Junko 群馬大学, 医学部, 准教授 (60208832) ; SASAKI Atsushi 埼玉医科大学, 医学部, 教授 (80225862) ; YOKOO Hideaki 群馬大学, 大学院・医学系研究科, 准教授 (40282389) ; ISHIUCHI Syogo 琉球大学, 医学部, 教授 (10312878)
• Project Period (FY): 2007 – 2010
• Keywords: 脳腫瘍 / 画像解析 / 遺伝子異常 / 病理診断 / 生物活性

Research Abstract

We analyzed the features of brain tumors from the view point of tissue and cellular morphology, phenotypic expression, and genetic alterations. We found that small round cells expressing nuclear transcription factor Olig2 are commonly exist in diffuse astrocytoma, oligoastrocytoma, oligodendroglioma, pilocytic astrocytoma, and glioneuronal tumors. These cells are presumed to be the progenitor cells of brain tumors. As molecular biologic markers, our analysis has shown that GFAP, Olig2, nestin, and NFP are important at protein level, and IDH1, p53, EGFR, 1p/19q, and INI-1 are crucial in genetic alterations. We have established the basis of morphologic molecular classification of brain tumors by fusion of the molecular events and histopathological diagnosis.

Research Products

• [Journal Article] Alterations in the RB1 pathway in low-grade diffuse gliomas lacking common genetic alterations. (2011)
  • Author(s): Kim YH, Lachuer J, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K, Sure U, Wrede K, Nobusawa S, Nakazato Y, Tanaka Y, et al
  • Journal Title: Brain Pathology (DOI:10.1111/j.1750-3639.2011.00492.x)
  • Peer Reviewed
• [Journal Article] High-throughput immunohistochemical profiling of primary brain tumors and non-neoplastic systemic organs with a specific antibody against the mutant isocitrate dehydrogenase 1 R132H protein. (2011)
  • Author(s): Ikota H, Nobusawa S, Tanaka Y, Yokoo H, Nakazato Y
  • Journal Title: Brain Tumor Pathol 28 Pages: 107-114
  • Peer Reviewed
• [Journal Article] Clinico-pathological feature of pilomyxoid astrocytomas : Three case reports. (2011)
  • Author(s): Nagaishi M, Yokoo H, Hirato J, Yoshimoto Y, Nakazato Y
  • Journal Title: Neuropathology 31 Pages: 152-157
  • Peer Reviewed
• [Journal Article] Clinicopathological and immunohistochemical study of 20 choroid plexus tumors : their histological diversity and the expression of markers useful for differentiation from metastatic cancer. (2011)
  • Author(s): Ikota H, Tanaka Y, Yokoo H, Nakazato Y
  • Journal Title: Brain Tumor Pathol (DOI:10.1007/s10014-011-0024-6)
  • Peer Reviewed
• [Journal Article] An immunohistochemical finding in glioneuronal lesions associated with epilepsy : The appearance of nestin-positive, CD34-positive and tau-accumulating cells. (2011)
  • Author(s): Nagaishi M, Arai M, Osawa T, Yokoo H, Hirato J, Yoshimoto Y, Nakazato Y
  • Journal Title: Neuropathology (doi:10.1111/j.1440-1789.2010.01188.x.)
  • Peer Reviewed
• [Journal Article] Molecular classification of low-grade diffuse gliomas. (2010)
  • Author(s): Kim YH, Nobusawa S, Mittelbronn M, Paulus W, Brokinkel B, Keyvani K, Sure U, Wrede K, Nakazato Y, Tanaka Y, et al
  • Journal Title: Am J Pathol 177 Pages: 2708-2714
  • Peer Reviewed
• [Journal Article] Expression of hydroxyindole-O-methyltransferase enzyme in the human central nervous system and in pineal parenchymal cell tumors. (2010)
  • Author(s): Fukuda T, Akiyama N, Ikegami M, Takahashi H, Sasaki A, Oka H, Komori T, Tanaka Y, Nakazato Y, et al
  • Journal Title: J Neuropathol Exp Neurol 69 Pages: 498-510
  • Peer Reviewed
• [Journal Article] Polar spongioblastoma : A high-grade glioma that does not contain the IDH1 mutation or 1p/19q LOH. (2010)
  • Author(s): Nagaishi M, Tanaka Y, Iwatate K, Yokoo H, Ueki K, Hyodo A, Nakazato Y
  • Journal Title: Neuropathology 30 Pages: 547-552
  • Peer Reviewed
• [Journal Article] Quantitative analysis of mitotic Olig2 cells in adult human brain and gliomas : implications for glioma histogenesis and biology. (2009)
  • Author(s): Rhee W, Ray S, Yokoo H, et al
  • Journal Title: Glia 57 Pages: 510-523
  • Peer Reviewed
• [Journal Article] Cerebral tumor with extensive rhabdoid features and a favorable prognosis. (2009)
  • Author(s): Ohba S, Yoshida K, Hirose Y, Ikeda E, Nakazato Y, Kawase T
  • Journal Title: J Neurosurg 111 Pages: 492-496
  • Peer Reviewed
• [Journal Article] A rosette-forming glioneuronal tumor of the spinal cord : the first case of a rosette-forming glioneuronal tumor originating from the spinal cord. (2009)
  • Author(s): Anan M, Inoue R, Ishii K, Abe T, Fujiki M, Kobayashi H, Goya T, Nakazato Y
  • Journal Title: Hum Pathol 40 Pages: 898-901
  • Peer Reviewed
• [Journal Article] Immunohistochemical and ultrastructural characterization of brain tumors in S100 beta-v-erbB transgenic rats. (2008)
  • Author(s): Yokoo H, Tanaka Y, Nobusawa S, Nakazato Y, Ohgaki H
  • Journal Title: Neuro-pathology 28 Pages: 591-598
  • Peer Reviewed
• [Journal Article] Diversity of glial cell components in pilocytic astrocytoma. (2008)
  • Author(s): Tanaka Y, Sasaki A, Ishiuchi S, Nakazato Y
  • Journal Title: Neuropathology 28 Pages: 399-407
  • Peer Reviewed
• [Journal Article] Low grade diffuse gliomas : Shared cellular composi-tion and morphometric differences. (2008)
  • Author(s): Kinjo S, Hirato J, Nakazato Y
  • Journal Title: Neuro-pathology 28 Pages: 455-465
  • Peer Reviewed
• [Journal Article] Ca2+-permeable AMPA receptors regulate growth of human glioblastoma via Akt activation. (2007)
  • Author(s): Ishiuchi S, Yoshida Y, Sugawara K, Aihara M, Ohtani T, Watanabe T, Saito N, Tsuzuki K, Okado H, Miwa A, Nakazato Y, Ozawa S
  • Journal Title: J Neurosci 27 Pages: 7987-8001
  • Peer Reviewed
• [Presentation] 脳腫瘍のWHO分類-その特徴と問題点- (2010)
  • Author(s): 中里洋一
  • Organizer: 脳腫瘍2010
  • Place of Presentation: 大阪市
  • Year and Date: 20100601-20100608
• [Presentation] 再発を繰り返し、最終的に偽乳頭状構造が明瞭となった中枢神経系hemangiopericytomaの1剖検例 (2010)
  • Author(s): 平戸純子、金城佐和子、宮永朋実、新井秀雄、横尾英明、中里洋一
  • Organizer: 第28回日本脳腫瘍病理学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-05-22
• [Presentation] 脳腫瘍のWHO分類(WHO2007) (2010)
  • Author(s): 中里洋一
  • Organizer: 第28回日本脳腫瘍病理学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-05-22
• [Presentation] S100β-v-erbBトランスジェニックラットに発生するグリオーマははNG2/CSPG4を発現する (2010)
  • Author(s): 横尾英明、田中優子、信澤純人、永石雅也、中里洋一、Hiroko Ohgaki
  • Organizer: 第28回日本脳腫瘍病理学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-05-21
• [Presentation] LAMP法を用いたグリオーマにおけるIDH1遺伝子変異の検出 (2010)
  • Author(s): 横尾英明、新井基展、中里洋一
  • Organizer: 第99回日本病理学会
  • Place of Presentation: 東京都
  • Year and Date: 2010-04-28
• [Presentation] 星細胞腫grade3/4に対する第II相臨床試験(JCOG0305)における病理中央診断の意義 (2009)
  • Author(s): 渋井壮一郎、嘉山孝正、中里洋一、他
  • Organizer: 第27回日本脳腫瘍病理学会
  • Place of Presentation: 福岡市
  • Year and Date: 2009-05-08
• [Presentation] 脳腫瘍の摘出から17年後、骨髄への広範な転移を起こし死亡したanaplastic oligo dendrogliomaの1例 (2009)
  • Author(s): 田中優子、伊藤秀明、平戸純子、中里洋一
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2009-05-01
• [Presentation] 脳腫瘍分類(WHO)とグリア系腫瘍 (2009)
  • Author(s): 中里洋一
  • Organizer: 第23回平野朝雄教授神経病理セミナー
  • Place of Presentation: 京都市
  • Year and Date: 2009-04-18
• [Presentation] Olig2-positive small round cells in glial and glioneuronal tumors. (2008)
  • Author(s): Nakazato Y, Tanaka Y, Miyanaga T, Yokoo H, Hirato J
  • Organizer: 27^<th> International Congress of the International Academy of Pathology.
  • Place of Presentation: Athens, Greece
  • Year and Date: 2008-10-15
• [Presentation] INI-1不活性化の有無からみた中枢神経系rhabdoid tumorの臨床病理学的特徴 (2008)
  • Author(s): 平戸純子、中里洋一
  • Organizer: 第26回日本脳腫瘍病理学会
  • Place of Presentation: 東京都
  • Year and Date: 2008-05-24
• [Presentation] 改訂された脳腫瘍WHO分類-新しい腫瘍型の病理を中心に- (2008)
  • Author(s): 中里洋一
  • Organizer: 第26回日本脳腫瘍病理学会特別講演
  • Place of Presentation: 東京都
  • Year and Date: 2008-05-23
• [Presentation] Diffuse astrocytomaの疾患概念と病理学的多様性 (2008)
  • Author(s): 中里洋一、金城佐和子、田中優子
  • Organizer: 第28回日本脳神経外科コングレスシンポジウム
  • Place of Presentation: 横浜市
  • Year and Date: 2008-05-09
• [Presentation] オリゴデンドログリオーマ細胞の形態と分化 (2007)
  • Author(s): 中里洋一
  • Organizer: 第25回日本脳腫瘍病理学会シンポジウム
  • Place of Presentation: 熊本市
  • Year and Date: 2007-04-19
• [Book] 脳腫瘍取扱い規約-臨床と病理カラーアトラス-第3版(日本脳神経外科学会・日本病理学会(編))(「脳腫瘍の分類」、「脳腫瘍マーカー」、「細胞診」、「組織学的分類」、「TUMORS OF NEUROEPITHELIAL TISSUE 神経上皮性腫瘍」) (2010)
  • Author(s): 中里洋一
  • Total Pages: 2-7, 26-34, 50-53, 88-92, 93-129
  • Publisher: 金原出版
• [Book] 新時代の脳腫瘍学-診断・治療の最前線-((編)松谷雅生)(脳腫瘍のWHO分類-現状と展望-) (2010)
  • Author(s): 中里洋一
  • Total Pages: 120-126
  • Publisher: 日本臨床社
• [Book] Annual Review神経2010((編)鈴木則宏、他)(WHO brain tumor classification 2007) (2010)
  • Author(s): 中里洋一
  • Total Pages: 27-37
  • Publisher: 中外医学社
• [Book] Annual Review神経2008((編)柳澤信夫、他)(Gliomatosis cerebriの病態) (2010)
  • Author(s): 中里洋一
  • Total Pages: 27-37
  • Publisher: 中外医学社
• [Book] 脳腫瘍臨床病理カラーアトラス第3版((編)河本圭司,吉田純,中里洋一)(「脳腫瘍の組織分類」、「Desmoplastic infantile astrocytoma/ganglioglioma」、「Pineocytoma」、「Pineal parenchymal tumor of intermediate differentiation」、「Pineoblastoma」、「Meningioma grade III. Anaplastic, papillary, rhabdoid meningioma」、「Paraganglioma」、「脳腫瘍の免疫組織化学」) (2009)
  • Author(s): 中里洋一
  • Total Pages: 7-11, 68-69, 80-81, 82-83, 84, 117-119, 143, 180-181
  • Publisher: 医学書院
• [Book] WHO Classification of Tumours of the Central Nervous System. 4^<th> ed.(Louis DN, et al.(eds))("Diffuse astrocytoma", "Glioblastoma", "Papillary glioneuronal tumour", "Pineocytoma", "Pineal parenchymal tumour of intermediate differentiation", "Pineoblastoma", "Papillary tumour of the pineal region", "CNS germ cell tumours") (2007)
  • Author(s): Nakazato Y, et al
  • Total Pages: 25-29, 33-49, 113-114, 122-123, 124-125, 126-127, 128-129, 198-204
  • Publisher: International Agency for Research on Cancer