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Prognostic stratification of patients with anaplastic gliomas according to genetic profile

  1. Caroline Dehais MD1,2,3,
  2. Florence Laigle-Donadey MD4,
  3. Yannick Marie MSc1,2,3,
  4. Michele Kujas MD5,
  5. Julie Lejeune PhD4,
  6. Alexandra Benouaich-Amiel MD1,2,3,4,
  7. Marta Pedretti MD1,2,3,
  8. Marc Polivka MD6,
  9. Khe-Hoang Xuan MD, PhD1,2,3,4,
  10. Joelle Thillet PhD1,2,3,
  11. Jean-Yves Delattre MD1,2,3,4,
  12. Marc Sanson MD, PhD1,2,3,4,†,*

Article first published online: 19 SEP 2006

DOI: 10.1002/cncr.22211

Issue

Cancer

Cancer

Volume 107, Issue 8, pages 1891–1897, 15 October 2006

Additional Information

How to Cite

Dehais, C., Laigle-Donadey, F., Marie, Y., Kujas, M., Lejeune, J., Benouaich-Amiel, A., Pedretti, M., Polivka, M., Xuan, K.-H., Thillet, J., Delattre, J.-Y. and Sanson, M. (2006), Prognostic stratification of patients with anaplastic gliomas according to genetic profile. Cancer, 107: 1891–1897. doi: 10.1002/cncr.22211

Author Information

  1. 1

    INSERM U711, Biologie des Interactions Neurones et Glie, Paris, France

  2. 2

    Universite Pierre et Marie Curie, Faculte de Medecine, Paris, France

  3. 3

    Groupe Hospitalier Pitie-Salpetriere, Paris, France

  4. 4

    Service de Neurologie Mazarin, Assistance Publique Hopitaux de Paris, Group Hospitalier, Salpetriere, Paris, France

  5. 5

    Laboratoire de Neuropathologie R. Escourolle, Assistance Publique Hopitaux de Paris, Group Hospitalier, Pitie-Salpetriere, Paris, France

  6. 6

    Service d'anatomopathologie, Hopital Lariboisiere, Paris, France

  1. †

    Fax: (011) 33 142160375

*Service de Neurologie Mazarin, Groupe Hospitalier Pitie-Salpetriere, 47 Boulevard de l'Hopital, 75013 Paris, France

Publication History

  1. Issue published online: 3 OCT 2006
  2. Article first published online: 19 SEP 2006
  3. Manuscript Accepted: 14 JUL 2006
  4. Manuscript Revised: 6 JUL 2006
  5. Manuscript Received: 25 MAY 2006

Funded by

  • Delegation a la Recherche Clinique. Grant Number: AP-HP Grant MUL 03012
  • Ligue Nationale Contre le Cancer, comite d'Ille et Vilaine

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Keywords:

  • anaplastic gliomas;
  • EGFR;
  • p53;
  • 1p;
  • 19q;
  • recursive partitioning analysis

Abstract

BACKGROUND.

There is a need to improve the current, controversial, and poorly reproducible classification of anaplastic gliomas, which represent a highly heterogeneous entity in terms of survival.

METHODS.

The impact of the most common genetic alterations on survival was investigated based on 156 anaplastic gliomas: Among the patients who were included, the gender ratio was 1.32, the median age was 45.5 years (range, 20–83 years), and the median Karnofsky performance status was 70 (range, 40–100). Genetic analysis included a search for loss of heterozygosity (LOH) on chromosomes 1p and 19q; amplification of chromosomes 9p and 10q and of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4) and mouse double-minute (MDM2) genes; and p53 expression.

RESULTS.

The median survival was 33.5 months, and the median progression-free survival was 15.8 months. In a univariate analysis, LOH on 1p and 19q was correlated with longer survival, whereas p53 expression, LOH on 9p, LOH on 10q, amplified EGFR, and deleted CDKN2A were correlated with shorter survival. LOH on 1p and 19q were associated with oligodendrogliomas, LOH on 10q was related to EGFR amplification, and LOH on 1p and 19q was mutually exclusive with EGFR amplification and LOH on 10q. In a multivariate analysis, the significant prognostic factors were age, histology, LOH on 1p and 19q, and P16/CDKN2A deletion. Recursive partitioning analysis (RPA) divided the whole group hierarchically into 3 distinct prognostic subgroups: Group A with 1p19q codeletion (median survival, 98 months), Group B with EGFR amplification (median survival, 17 months), and Group CC (median survival, 31 months), providing a basis for a genetically based prognostic subclassification for patients with Grade III gliomas.

CONCLUSIONS.

The search for 1p19q codeletion and EGFR receptor amplification provides a simple, clinically relevant prognostic subclassification of grade III gliomas. Cancer 2006. © 2006 American Cancer Society.

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