title: Diagnostic and prognostic value of alpha internexin expression in a series of 409 gliomas.
abstract: The neuronal intermediate filament alpha internexin (INA) is expressed in most gliomas with 1p19q codeletion and could represent a valuable prognostic marker in clinical routine. INA expression was analysed on 409 gliomas and correlated with histology, progression free survival (PFS), overall survival (OS), genomic profile assessed by CGH-array, IDH1/IDH2 mutation and p53 expression. INA was expressed in 59% of grade II oligodendrogliomas (n=73), 45% of grade III oligodendrogliomas (n=133), 15% of grade II oligoastrocytomas (n=61), 12% of grade III oligoastrocytomas (n=41), 23% of glioblastomas with oligodendroglial component (n=31), 0% of grade I astrocytomas (n=3), 0% of grade II astrocytomas (n=14), 6% of grade III astrocytomas (n=17) and 0% of glioblastomas (n=36). INA expression was detected in 85% of gliomas with complete 1p19q codeletion ('true 1p19q signature') (n=85) versus 15% of gliomas without 1p19q codeletion (n=245), including 14% of gliomas with variable/partial 1p19q deletion ('false 1p19q signature') (n=72) (p<0.0001). INA was expressed by 43% of gliomas with IDH1 mutation (n=197) versus 12% of gliomas without IDH1 mutation (n=156) (p<0.0001). In oligodendroglial gliomas (n=240), INA expression specificity for 1p19q codeletion was 80%, sensitivity 85%, positive predictive value 70%, and negative predictive value was 91%. Combining INA and p53 expressions improved INA predictive accuracy for 1p19q codeletion. In grade III gliomas, INA expression was associated with longer PFS (42.1 versus 10.2 months, p=0.0007) and longer OS (124.6 versus 20.6 months, p=0.0001). In conclusion, INA expression is a fast, cheap and reliable prognostic marker, and represents a surrogate marker for 1p19q complete codeletion.
authors.affiliation: Hôpital Neurologique, Service de Neurologie B, Lyon, France.
authors.forename: François
authors.initials: F
authors.lastname: Ducray
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Crinière
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.forename: Sophie
authors.initials: S
authors.lastname: Paris
authors.forename: Catherine
authors.initials: C
authors.lastname: Carpentier
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Dieme
authors.forename: Clovis
authors.initials: C
authors.lastname: Adam
authors.forename: Khe
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005910:Glioma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; D016159:Tumor Suppressor Protein p53; C046643:alpha-internexin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human