title: Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas.
abstract: Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ogura
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsukamoto
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Natsumeda
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Isogawa
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Neurosurgery, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: IDH1; MGMT; glioma; immunohistochemistry; p53