Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations

Dominique Figarella-Branger, Karima Mokhtari, Caroline Dehais, Anne Jouvet, Emmanuelle Uro-Coste, Carole Colin, Catherine Carpentier, Fabien Forest, Claude Alain Maurage, Jean Michel Vignaud, Marc Polivka, Emmanuelle Lechapt-Zalcman, Sandrine Eimer, Gabriel Viennet, Isabelle Quintin-Roué, Marie Hélène Aubriot-Lorton, Marie Danièle Diebold, Delphine Loussouarn, Catherine Lacroix, Valérie RigauAnnie Laquerrière, Fanny Vandenbos, Sophie Michalak, Henri Sevestre, Michel Peoch, François Labrousse, Christo Christov, Jean Louis Kemeny, Marie Pierre Chenard, Danchristian Chiforeanu, François Ducray, Ahmed Idbaih, Christine Desenclos, Philippe Menei, Edmond Al Nader, Joel Godard, Stéphanie Servagi-Vernat, Antoine Carpentier, Hugues Loiseau, Phong Dam-Hieu, Jean Sebastien Guillamo, Evelyne Emery, Pierre Verelle, Xavier Durando, Thierry Faillot, Caroline Le Guerinel, François Ghiringhelli, Fabrice Parker, Clovis Adam, François Dubois, Carole Ramirez, Edouard Marcel Gueye, Jerome Honnorat, Olivier Chinot, Luc Bauchet, Patrick Beauchesne, Mario Campone, Jean Sébastien Frenel, Denys Fontaine, Chantal Campello, Pascal Roger, Anne Heitzmann, Mélanie Fesneau, Jean Yves Delattre, Selma Elouadhani-Hamdi, Damien Ricard, Philippe Colin, Elodie Vauléon, Olivier Langlois, Marie Janette Motsuo Fotso, Marie Andraud, Servane Mouton, Georges Noel, Nicolas Desse, Raoulin Soulard, Elisabeth Cohen-Moyal, Vincent Lubrano, Frederic Dhermain

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    Résumé

    Background. The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). Methods. The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. Results. 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10-4), IDH1/2 mutation (P < 10-4), chromosome 4 loss (P < 10-3), and better overall survival (P < 10 -4). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival ( P = .024) and shorter overall survival ( P = .023). Conclusions. The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.

    langue originaleAnglais
    Pages (de - à)1244-1254
    Nombre de pages11
    journalNeuro-Oncology
    Volume16
    Numéro de publication9
    Les DOIs
    étatPublié - 1 janv. 2014

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