title: Detection of IDH1 mutation in human gliomas: comparison of immunohistochemistry and sequencing.
abstract: Isocitrate dehydrogenase 1 (IDH1) mutations have recently been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas, as well as secondary glioblastomas, whereas primary glioblastomas very rarely contain IDH1 mutations. Furthermore, a specific monoclonal antibody, IMab-1, which recognizes IDH1-R132H-the most frequent IDH1 mutation-has been generated. IMab-1 has been reported to react with the IDH1-R132H protein, but not the wild-type IDH1 or the other IDH1 mutant proteins in Western-blot analysis. However, the importance of immunohistochemistry using IMab-1 has not yet been elucidated. In this study, we compared the findings from IMab-1 immunohistochemistry and direct DNA sequencing using 49 glioma samples. IMab-1 detected 12 out of 49 cases; however, only nine cases were found to be IDH1-R132H by direct DNA sequencing because of a small population of IDH1-R132H mutation-possessing tumor cells, indicating that IMab-1 immunohistochemistry is useful for detecting IDH1-R132H. We conducted immunohistochemical detection in 52 cases of grade III astrocytomas. The median time to progression (TTP) was significantly longer in the cases with the IDH1 mutation (86.7 months) compared to the cases without the IDH1 mutation (wild type, 10.4 months) (p < 0.01). In conclusion, the anti-IDH1-R132H-specific monoclonal antibody IMab-1 is very useful for detecting IDH1-R132H in immunohistochemistry, and predicting the time to progression in grade III anaplastic astrocytomas. Therefore, IMab-1 is likely to be useful for the diagnosis of mutation-bearing gliomas and for determining the treatment strategy of grade III gliomas.
authors.affiliation: Department of Neurosurgery, Institute of Clinical Medicine,University of Tsukuba, 1-1-1 Tennoudai, Tsukuba,Ibaraki 305-8575, Japan. shingo4@md.tsukuba.ac.jp
authors.forename: Shingo
authors.initials: S
authors.lastname: Takano
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Masahide
authors.initials: M
authors.lastname: Matsuda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Mika Kato
authors.initials: MK
authors.lastname: Kaneko
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Kato
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D007521:Isocitrate Dehydrogenase / Q000032:analysis / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D009837:Oligodendroglioma / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D050505:Mutant Proteins; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human