Histological and molecular classification of gliomas

Gliomas are the most frequent tumors of the central nervous system. The WHO classification, based on the presumed cell origin, distinguishes astrocytic, oligodendrocytic and mixed gliomas. A grading system is based on the presence of the following criteria: increased cellular density, nuclear atypias, mitosis, vascular proliferation and necrosis. The main histological subtype of grade I gliomas are pilocytic astrocytomas, which are benign. Diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas are low-grade (II) or high-grade (III and IV) tumors. Glioblastomas correspond to grade IV astrocytomas. C. Daumas-Duport et al. have proposed another classification based on histology and imaging data, which distinguishes oligodendrogliomas and mixed gliomas of grade A (without endothelial proliferation and/or contrast enhancement), oligodendrogliomas and mixed gliomas of grade B (with endothelial proliferation or contrast enhancement), glioblastomas and glioneuronal malignant tumors. Both classifications lack reproducibility. Many studies have searched for a molecular classification. Recurrent abnormalities in gliomas have been found. They encompassed recurrent chromosomal alterations, such as lost of chromosome 10, gain of chromosome 7, deletion of chromosome 1p and 19q, but also activation of the Akt pathway (amplification of EGFR), dysregulation of the cell cycle (deletion of p16, p53). These studies have enabled the description of two molecular subtypes for glioblastomas. De novo glioblastomas, which occur in young patients without of a prior history of brain tumor and harbor frequent amplification of EGFR, deletion of p16 and mutation of PTEN while mutation of p53 is infrequent. Secondary glioblastomas occur in the context of a preexisting low-grade glioma and are characterized by more frequent mutation of p53. On the other side, combined complete deletion of 1p and 19q as the result of the translocation t(1;19)(q10;p10) is highly specific of oligodendrogliomas. However, histological and molecular classifications do not always correspond as many alterations are shared by high-grade tumors, whatever their histological type. Besides, few molecular alterations have a prognostic value. Among them combined 1p19q loss is associated with a better prognosis and response to treatment for oligodendrogliomas. Another promising marker is MGMT, a DNA repairing enzyme. If inactivated (by methylation of the promoter of the gene) a better sensitivity is observed with nitrosoure agents. However, some concerns exist for the method of detection of this abnormality. Quality control for molecular techniques is also required before using them for therapeutic strategy. In the future, studies of gene expression profiles by cDNA-microarray as well as works in the field of neural progenitor cells will probably provide new insights in gliomagenesis. (C) 2008 Elsevier Masson SAS. Tous droits reserves.