title: Prognostic stratification of gliomatosis cerebri by IDH1 R132H and INA expression.
abstract: Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.
authors.affiliation: AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Neuropathology Laboratory R Escourolle, 75013, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Desestret
authors.forename: Pietro
authors.initials: P
authors.lastname: Ciccarino
authors.forename: François
authors.initials: F
authors.lastname: Ducray
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Crinière
authors.forename: Blandine
authors.initials: B
authors.lastname: Boisselier
authors.forename: Marianne
authors.initials: M
authors.lastname: Labussière
authors.forename: Marc
authors.initials: M
authors.lastname: Polivka
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.forename: Gentian
authors.initials: G
authors.lastname: Kaloshi
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Khe
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism*; D018302:Neoplasms, Neuroepithelial / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D007381:Intermediate Filament Proteins; D050505:Mutant Proteins; C046643:alpha-internexin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human