title: Immunohistochemical detection of IDH1 mutation, p53, and internexin as prognostic factors of glial tumors.
abstract: Isocitrate dehydrogenase 1 (IDH1) mutations, which are early and frequent genetic alterations in astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas, are specific to arginine 132 (R132). Recently, we established monoclonal antibodies (mAbs) against IDH1 mutations: anti-IDH1-R132H and anti-IDH1-R132S. However, the importance of immunohistochemistry using the combination of those mAbs has not been elucidated. For this study, 164 cases of glioma were evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti-IDH1 mAbs (HMab-1 and SMab-1). IDH1 mutation was detected, respectively, in 9.7%, 63.6%, 51.7%, and 77.8% of primary grade IV, secondary grade IV, grade III, and grade II gliomas. For each grade of glioma, prognostic factors for progression-free survival and overall survival were evaluated using clinical and pathological parameters in addition to IDH1 immunohistochemistry. IDH1 mutation, p53 overexpression, and internexin expression, as evaluated using immunohistochemistry with clinical parameters such as degree of surgical removal and preoperative Karnofsky Performance Status (KPS), might be of greater prognostic significance than histological grading alone in grade III as well as IDH1 mutation in grade IV gliomas.
authors.affiliation: Department of Neurological Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, 305-8575, Ibaraki, Tsukuba, Japan. shingo4@md.tsukuba.ac.jp
authors.forename: Shingo
authors.initials: S
authors.lastname: Takano
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Mika Kato
authors.initials: MK
authors.lastname: Kaneko
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsujimoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Matsuda
authors.forename: Kei
authors.initials: K
authors.lastname: Nakai
authors.forename: Ryo
authors.initials: R
authors.lastname: Yanagiya
authors.forename: Shunpei
authors.initials: S
authors.lastname: Morita
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007114:Immunization; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D010446:Peptide Fragments / Q000276:immunology; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D007381:Intermediate Filament Proteins; D010446:Peptide Fragments; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C046643:alpha-internexin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human