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. 2014 Sep;16(9):1244-54.
doi: 10.1093/neuonc/nou047. Epub 2014 Apr 9.

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

Dominique Figarella-Branger  1 , Karima Mokhtari  1 , Caroline Dehais  1 , Anne Jouvet  1 , Emmanuelle Uro-Coste  1 , Carole Colin  1 , Catherine Carpentier  1 , Fabien Forest  1 , Claude-Alain Maurage  1 , Jean-Michel Vignaud  1 , Marc Polivka  1 , Emmanuelle Lechapt-Zalcman  1 , Sandrine Eimer  1 , Gabriel Viennet  1 , Isabelle Quintin-Roué  1 , Marie-Hélène Aubriot-Lorton  1 , Marie-Danièle Diebold  1 , Delphine Loussouarn  1 , Catherine Lacroix  1 , Valérie Rigau  1 , Annie Laquerrière  1 , Fanny Vandenbos  1 , Sophie Michalak  1 , Henri Sevestre  1 , Michel Peoch  1 , François Labrousse  1 , Christo Christov  1 , Jean-Louis Kemeny  1 , Marie-Pierre Chenard  1 , Danchristian Chiforeanu  1 , François Ducray  1 , Ahmed Idbaih  1 ; POLA Network
Collaborators, Affiliations

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

Dominique Figarella-Branger et al. Neuro Oncol. 2014 Sep.

Abstract

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.

Keywords: 1p/19q codeletion; anaplastic oligodendrogliomas; microvascular proliferation; mitoses; necrosis.

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Figures

Fig. 1.
Fig. 1.
Pathological features of the 3 subgroups of anaplastic oligodendrogliomas. (a–c) Anaplastic oligodendroglioma with high mitotic count but no microvascular proliferation (MVP) and no palisading necrosis (PN). (a) Nodule of high cell density (hematoxylin-eosin [HE], left) with a KI 67 labeling index of 12% (immunostaining, right). (b) Higher magnification showing 3 mitotic figures (arrows) within one HPF (HE). (c) Anaplastic oligodendroglioma characterized by MVP (HE). (d) Anaplastic oligodendroglioma characterized by MVP and PN (*, HE). (e and f) Characteristic pattern of IDH1R132H (e) and internexin alpha (f) immunostaining in the same case recorded in panel a and b. Scale bar = 50 µm.
Fig. 2.
Fig. 2.
(a) INA expression, (b) IDH mutation, and (c) 1p/19q status (c) are associated with longer progression-free survival and overall survival in anaplastic oligodendrogliomas.
Fig. 3.
Fig. 3.
Number of chromosomal arm alterations (>4) predicts shorter progression-free survival and overall survival in the whole group of anaplastic oligodendrogliomas (a) and in 1p/19q codeleted anaplastic oligodendrogliomas (b).
See this image and copyright information in PMC

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