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

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Date publication

septembre 2014

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CHENARD Marie-Pierre, Pr VIGNAUD Jean-Michel


Tous les auteurs :
Figarella-Branger D, Mokhtari K, Dehais C, Jouvet A, Uro-Coste E, Colin C, Carpentier C, Forest F, Maurage CA, Vignaud JM, Polivka M, Lechapt-Zalcman E, Eimer S, Viennet G, Quintin-Roue I, Aubriot-Lorton MH, Diebold MD, Loussouarn D, Lacroix C, Rigau V, Laquerriere A, Vandenbos F, Michalak S, Sevestre H, Peoch M, Labrousse F, Christov C, Kemeny JL, Chenard MP, Chiforeanu D, Ducray F, Idbaih A

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.

Référence

Neuro Oncol. 2014 Sep;16(9):1244-54