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.