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Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system

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Abstract

Adult grade II low-grade gliomas (LGG) are classified according to the WHO as astrocytomas, oligodendrogliomas or mixed gliomas. TP53 mutations and 1p19q codeletion are the main molecular abnormalities recorded, respectively, in astrocytomas and oligodendrogliomas and in mixed gliomas. Although IDH mutations (IDH1 or IDH2) are recorded in up to 85 % of low-grade gliomas, IDH negative gliomas do occur. We have searched for p53 expression, 1p19q codeletion and IDH status (immunohistochemical detection of the common R132H IDH1 mutation and IDH direct sequencing). Internexin alpha (INA) expression previously recorded to be associated with 1p19q codeletion (1p19q+) gliomas was also analysed. Low-grade gliomas were accurately classified into four groups: group 1, IDH+/p53−/1p19q−; group 2, IDH+/p53−/1p19q+; group 3, IDH+/p53+/1p19q−; and group 4, triple negative gliomas. In contrast to the WHO classification, this molecular classification predicts overall survival on uni- and multivariate analysis (P = 0.001 and P = 0.007, respectively). Group 4 carries the worst prognosis and group 2 the best. Interestingly, p53 +/INA− expression predicts lack of 1p19q codeletion (specificity 100 %, VPP 100 %). The combined use of these three molecular markers allow for an accurate prediction of survival in LGG. These findings could significantly modify LGG classification and may represent a new tool to guide patient-tailored therapy. Moreover, immunohistochemical detection of p53, INA and mR132H IDH1 expression could represent an interesting prescreening test to be performed before 1p19q codeletion, IDH1 minor mutation and IDH2 mutation detection.

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Acknowledgments

We are grateful to C. Bequet-Boucard and to C. Courdy for their help in the collection of data, to M. Barrié, neuro-oncologist, and to H. Dufour, S. Fuentes, JC. Peragut and F. Grisoli, neurosurgeons, for taking care of the patients. The AP-HM and the AP-HM tumor bank, authorization number 2008/70, are also acknowledged. This work was supported by institutional grants and by INCA grants (PROCAN, RS019, Gliother, PACA Canceropole) to D. Figarella-Branger, by the Association pour la Recherche sur les Tumeurs Cérébrales (ARTC-Sud), and by the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC).

Conflict of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Service d’Anatomie Pathologique et de Neuropathologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Dominique Figarella-Branger, Corinne Bouvier & André Maues de Paula

  2. INSERM, UMR 911, 13000, Marseille, France

    Dominique Figarella-Branger, Corinne Bouvier, Carole Colin & Philippe Metellus

  3. Faculté de Médecine, Aix-Marseille Université, 13000, Marseille, France

    Dominique Figarella-Branger, Corinne Bouvier, Carole Colin & Philippe Metellus

  4. Service de neuropathologie Raymond Escourolle, Groupe hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013, Paris, France

    Karima Mokhtari

  5. CRICM, UMR-S975, Université Pierre et Marie Curie, Paris 6, 75013, Paris, France

    Karima Mokhtari

  6. Unité d’Aide méthodologique à la Recherche Clinique et Epidémiologique, DRRC, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Anderson Loundou

  7. Unité de Neurooncologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Olivier Chinot

  8. Service de Neurochirurgie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, 13000, Marseille, France

    Philippe Metellus

  9. Service de Neurochirurgie, APHM, CHU Timone, 264 rue Saint-Pierre, 13385, Marseille cedex 05, France

    Philippe Metellus

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  1. Dominique Figarella-Branger
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  2. Corinne Bouvier
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  3. André Maues de Paula
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Correspondence to Philippe Metellus.

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Figarella-Branger, D., Bouvier, C., de Paula, A.M. et al. Molecular genetics of adult grade II gliomas: towards a comprehensive tumor classification system. J Neurooncol 110, 205–213 (2012). https://doi.org/10.1007/s11060-012-0953-x

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  • DOI: https://doi.org/10.1007/s11060-012-0953-x

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