title: 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.
authors.affiliation: Service d'Anatomie Pathologique et de Neuropathologie, Hôpital de la Timone, APHM, Marseille, France.|INSERM, CRO2 UMR_S 911, Aix-Marseille Université, Marseille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.affiliation: Département de Neuropathologie Raymond Escourolle, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.|Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), UMR 7225, Université Pierre et Marie Curie-Paris 6, Paris, France.|INSERM U1127, Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.affiliation: INSERM, CRO2 UMR_S 911, Aix-Marseille Université, Marseille, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Colin
authors.affiliation: Service d'Anatomie Pathologique et Histologie-Cytologie, Hôpital Rangueil, CHU Toulouse, Toulouse, France.|INSERM U1037, Centre de Recherche en Cancérologie de Toulouse, Université de Toulouse, Toulouse, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Uro-Coste
authors.affiliation: Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon, Bron, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Jouvet
authors.affiliation: Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dehais
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), UMR 7225, Université Pierre et Marie Curie-Paris 6, Paris, France.|INSERM U1127, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Carpentier
authors.affiliation: Département de Neuropathologie Raymond Escourolle, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.|Service d'Anatomie Pathologique, Hôpital Foch, Suresnes, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.affiliation: Service Anatomie Pathologique, Pôle Pathologie Biologique, CHU Lille, Lille, France.
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Maurage
authors.affiliation: Service de Pathologie-Neuropathologie, Hôpital Pellegrin, CHU Bordeaux, Bordeaux, France.|EA2406, Histologie et Pathologie Moléculaire des Tumeurs, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Eimer
authors.affiliation: Service d'Anatomie et Cytologie Pathologique, Hôpital Lariboisière, AP-HP, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Polivka
authors.affiliation: Laboratoire d'Anatomie Pathologique, Hôpital Central, CHU Nancy, Nancy, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vignaud
authors.affiliation: Laboratoire de Pathologie, Hôpital Charles Nicolle, CHU Rouen, Rouen, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerriere
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, CHU Amiens, Amiens, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Sevestre
authors.affiliation: Service d'Anatomie Pathologique, Hôpital de la Côte de Nacre, CHU Caen, Caen, France.|GIP CYCERON, CERVOxy, UMR 6301 ISTCT, CNRS, Caen, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lechapt-Zalcman
authors.affiliation: Service Anatomie Pathologique, Hôpital de la Cavale Blanche, CHU Brest, Brest, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Quintin-Roué
authors.affiliation: Service Anatomie et Cytologie Pathologiques, Plateau Technique de Biologie G. Mack, CHU Dijon, Dijon, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Aubriot-Lorton
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital Robert Debré, CHU Reims, Reims, France.
authors.forename: Marie-Danièle
authors.initials: MD
authors.lastname: Diebold
authors.affiliation: Service Anatomie et Cytologie Pathologiques, Hôpital Jean Minjoz, CHU Besançon, Besançon, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Viennet
authors.affiliation: Service Anatomie et Cytologie Pathologiques, Hôpital Bicêtre, AP-HP, Kremlin-Bicêtre, France.
authors.forename: Clovis
authors.initials: C
authors.lastname: Adam
authors.affiliation: Service d'Anatomie Pathologique B, Hôpital Laennec, CHU Nantes, Nantes, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Loussouarn
authors.affiliation: Département Pathologie Cellulaire et Tissulaire, CHU Angers, Angers, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Michalak
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital Gui de Chaulliac, CHU Montpellier, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Rigau
authors.affiliation: Service d'Anatomie Pathologique, Hôpital la Source, CHR Orléans, Orléans, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Heitzmann
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital Pasteur, CHU Nice, Nice, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Vandenbos
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, Hôpital Nord, CHU Saint-Etienne, Saint-Etienne, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Forest
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, Hôpital Pontchaillou, CHU Rennes, Renens, France.
authors.forename: Danchristian
authors.initials: D
authors.lastname: Chiforeanu
authors.affiliation: Service Anatomie Pathologique, Hôpitaux Civils de Colmar, Colmar, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Tortel
authors.affiliation: Service Anatomie Pathologique, Hôpital Dupuytren, CHU Limoges, Limoges, France.
authors.forename: François
authors.initials: F
authors.lastname: Labrousse
authors.affiliation: Service d'Anatomie Pathologique, Hôpital Hautepierre, CHU Strasbourg, Strasbourg, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.affiliation: Service Anatomie Pathologique, HIA Saint-Anne, Toulon, France.
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Nguyen
authors.affiliation: Département de Neuropathologie, CH Sainte-Anne, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Varlet
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Kemeny
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital la Milétrie, CHU Poitiers, Poitiers, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Levillain
authors.affiliation: Service d'Anatomie et Cytologie Pathologique, Hôpital Beaujon, AP-HP, Clichy, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Cazals-Hatem
authors.affiliation: Laboratoire d'Anatomie et Cytologie Pathologiques des Feuillants, Toulouse, France.
authors.forename: Pomone
authors.initials: P
authors.lastname: Richard
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), UMR 7225, Université Pierre et Marie Curie-Paris 6, Paris, France.|INSERM U1127, Paris, France.|Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005910:Glioma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D019394:Ki-67 Antigen; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: 1p/19q co-deletion; GBMO; IDH1 R132H immunoexpression; adult high-grade gliomas; necrosis