Prognostic Relevance of Histomolecular Classification of Diffuse Adult High-Grade Gliomas with Necrosis

Abstract

Diffuse adult high-grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO," restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co-deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10(-4) ). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co-deleted AO, IDH1 R132H-GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.

Keywords: 1p/19q co-deletion; GBMO; IDH1 R132H immunoexpression; adult high-grade gliomas; necrosis.

Figure 1

A–C. Anaplastic oligodendroglioma (AO) with focal necrosis. A. Oligodendroglial population with high cellularity, vascular proliferation and focal necrosis (asterisk) [hematoxylin and eosin (HE) ×100]. B. Perinuclear halo, moderate pleomorphism and hyperchromatism (HE ×400). C. Diffuse expression of IDH1 R132H (×400). D–G. Glioblastoma with oligodendroglial component (GBM/GBMO). D. Malignant glioma with high cellular pleomorphism and necrosis (asterisk) (HE ×100). E. On the left, tumor is composed of round cells with perinuclear halo and on the right by more pleomorphic cells (HE ×100). F. High magnification of oligodendroglial‐like component (HE ×400). G. High magnification of more classical GBM feature (HE ×400). H–J. Anaplastic oligoastrocytoma (AOA) with necrosis/GBMO. H. Mixture of oligodendroglial‐like and gemistocytic‐like cells with necrotic area (asterisk) (HE ×100). I. High magnification showing transitional appearances between oligodendroglial and astrocytic cells (HE ×400). J. Diffuse expression of IDH1 R132H (×400). K–M. AOA with necrosis/GBMO. K, L. Mixture of oligodendroglial cells and astrocytic cells usually pleomorphic with necrotic area (asterisk) (HE ×100). M. Diffuse expression of IDH1 R132H (×400).

Figure 2

A. Histological diagnosis distribution according to the three molecular subgroups defined regarding 1p/19q co‐deletion and IDH1 R132H expression status. B. EGFR amplification and p16 deletion status in these three molecular subgroups.

Figure 3

A–D. Histological subgroups display significant different progression free survival (PFS) and overall survival (OS): AO with 1p/19q co‐deletion (C, D) are associated with best prognosis. E–F. Three prognostically relevant molecular subgroups of patients can be defined on the basis of IDH1 R132H expression and 1p/19q co‐deletion status: IDH1 R132H positive and 1p/19q co‐deleted cases are associated with best prognosis.