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Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic
Dominique Figarella-Branger1, Karima Mokhtari1, Caroline Dehais1
1APHM, Hôpital de la Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France (D.F.-B.); Aix-Marseille Université, Inserm, CRO2 UMR_S 911, Marseille, France (D.F.-B., C.Co.); AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neuropathologie Raymond Escourolle, Paris, France (K.M., A.I.); Université Pierre et Marie Curie - Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), UMRS 975, Paris, France (K.M., C.Ca., A.I.); Inserm U975, Paris, France (K.M., C.Ca., A.I.); AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2 - Mazarin, Paris, France (C.D.); Centre de Pathologie et de Neuropathologie Est, Bron, France (A.J.); CHU Toulouse, Hôpital Rangueil, Service d'Anatomie Pathologique et Histologie-Cytologie, Toulouse, France (E.U.-C.); Inserm U1037, Centre de Recherche en Cancérologie de Toulouse, Université de Toulouse, France (E.U.-C.); CHU Saint-Etienne, Hôpital Nord, Service d'Anatomie et Cytologie Pathologiques, Saint-Etienne, France (F.F., M.P.); CHU Lille, Pôle Pathologie Biologique, Service Anatomie Pathologique, Lille, France (C.-A.M.); CHU Nancy, Hôpital Central, Laboratoire d'Anatomie Pathologique, Nancy, France (J.-M.V.); AP-HP, Hôpital Lariboisière, Service d'Anatomie et Cytologie Pathologique, Paris, France (M.P.); CHU Caen, Hôpital de la Côte de Nacre, Service d'Anatomie Pathologique, Caen, France (E.L.-Z.); CNRS, UMR 6301 ISTCT, CERVOxy, GIP CYCERON, Caen, France (E.L.-Z.); CHU Bordeaux, Hôpital Pellegrin, Service de Pathologie - Neuropathologie, Bordeaux, France (S.E.); EA2406, Histologie et Pathologie Moléculaire des Tumeurs, Université Bordeaux Segalen, Bordeaux, France (S.E.); CHU Besançon, Hôpital Jean Minjoz, Service Anatomie et Cytologie Pathologiques, Besançon, France (G.V.); CHU Brest, Hôpital de la Cavale Blanche, Service Anatomie Pathologique, Brest, France (I.Q.-R.); CHU Dijon, Plateau Technique de Biologie G. Mack, Service Anatomie et
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.
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