Molecular biomarkers and integrated pathological diagnosis in the reclassification of gliomas

Abstract

The present study aimed to evaluate the impact caused by the 2016 World Health Organization (WHO) diagnostic classification of gliomas in 139 patients studied in Argentina. Formalin-fixed paraffin-embedded tissues were used for histological and immunohistochemical analysis [glial fibrillary acidic protein, KI67, synaptophysin and isocitrate dehydrogenase (IDH)1-R132H]. DNA from formalin-fixed paraffin-embedded tissues was used for molecular analysis: 1p/19q co-deletion and mutation status of the IDH gene. These experiments were performed by direct Sanger sequencing and multiplex ligation-dependent probe amplification. According to the new classification, diagnoses included oligodendro-glioma IDH-mutant and 1p/19q co-deletion (4.20%), anaplastic oligodendroglioma IDH-mutant and 1p/19q co-deletion (2.52%), diffuse astrocytoma IDH-mutant (6.72%), diffuse astrocytoma IDH-wild type (1.68%), anaplastic astrocytoma IDH-mutant (5.04%), anaplastic astrocytoma IDH-wild type (8.40%), glioblastoma IDH-mutant (5.88%) and glioblastoma IDH-wild type (65.56%). Regarding tumor histology, 60% of oligodendrogliomas, 35% of astrocytoma and 100% of unclassified gliomas were re-classified, while glioblastomas maintained their initial classification. Additionally, the present study evaluated the prognostic value of the histological grade for the 2007 and 2016 WHO classifications of gliomas. The histological subgroup associated with longer overall survival (OS) was grade II glioma (OS-2007WHO, 35.6 months; and OS-2016WHO, 47.7 months). Glioblastoma was the subgroup associated with a poor outcome (OS-2007WHO, 10.4 months; and OS-2016WHO, 11.1 months). The present study evaluated the OS of tumor grade subgroups with respect to their IDH status. For all subgroups, IDH-mutant tumors were associ- ated with an improved prognosis compared with IDH-wild type tumors. The results suggested that the incorporation of molecular biomarkers in the new WHO classification improves tumor characterization and prognostic value of the subgroups.