Figarella-Branger Dominique, Mokhtari Karima, Colin Carole, Uro-Coste Emmanuelle, Jouvet Anne, Dehais Caroline, Carpentier Catherine, Villa Chiara, Maurage Claude-Alain, Eimer Sandrine, Polivka Marc, Vignaud Jean-Michel, Laquerriere Annie, Sevestre Henri, Lechapt-Zalcman Emmanuelle, Quintin-Roué Isabelle, Aubriot-Lorton Marie-Hélène, Diebold Marie-Danièle, Viennet Gabriel, Adam Clovis, Loussouarn Delphine, Michalak Sophie, Rigau Valérie, Heitzmann Anne, Vandenbos Fanny, Forest Fabien, Chiforeanu Danchristian, Tortel Marie-Claire, Labrousse François, Chenard Marie-Pierre, Nguyen Anh Tuan, Varlet Pascale, Kemeny Jean Louis, Levillain Pierre-Marie, Cazals-Hatem Dominique, Richard Pomone, Delattre Jean-Yves
Service d'Anatomie Pathologique et de Neuropathologie, Hôpital de la Timone, APHM, Marseille, France.
INSERM, CRO2 UMR_S 911, Aix-Marseille Université, Marseille, France.
Brain Pathol. 2015 Jul;25(4):418-28. doi: 10.1111/bpa.12227. Epub 2014 Dec 31.
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.
伴有坏死的弥漫性成人高级别胶质瘤（HGGs）包括伴有坏死的间变性少突胶质细胞瘤（AOs，Ⅲ级）、胶质母细胞瘤（GBM，Ⅳ级）以及具有少突胶质细胞成分的胶质母细胞瘤（GBMO，Ⅳ级）。在此，我们旨在探寻这些肿瘤的组织学分类及分子改变与预后的相关性。共纳入约210例患者（63例AO、56例GBM和91例GBMO）。GBMO组分为“伴有坏死的Ⅳ级间变性少突星形细胞瘤（AOA）/GBMO”，限于显示星形细胞和少突胶质细胞成分混合的肿瘤，以及基于呈现少突胶质细胞灶和GBM特征的肿瘤的“GBM/GBMO”。进行了基因组阵列、IDH1 R132H表达分析及IDH直接测序。1p/19q共缺失是AO的特征，而GBM和GBM/GBMO的特征是无IDH1 R132H表达且1p/19q完整。伴有坏死的AOA/GBMO主要表现为IDH1 R132H表达且1p/19q完整。其他IDH1或IDH2突变极为罕见。组织学和分子分类均能预测无进展生存期（PFS）和总生存期（OS）（P＜10⁻⁴）。伴有坏死的弥漫性成人HGGs可分为具有预后相关性的三个组织分子组：1p/19q共缺失的AO、IDH1 R132H野生型GBM以及1p/19q完整的IDH1 R132H突变型胶质瘤，后者可能归类为IDH1 R132H突变型GBM。由于组织分子异质性，我们建议去除GBMO这一名称。
