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Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas

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Abstract

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5±4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (<50 years) survived significantly longer than older patients (>50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma (P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (1p, 27%; 19q, 45%), rare in fibrillary astrocytomas (1p, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multivariate Cox’s regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

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Acknowledgements

This work was supported by a grant from the Foundation for Promotion of Cancer Research, Japan, and a grant from the Cancer Society of the Canton of Zurich (Zürcher Krebsliga), Switzerland.

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Authors and Affiliations

  1. International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France

    Yoshikazu Okamoto, Pier-Luigi Di Patre, Christoph Burkhard, Sonja Horstmann, Benjamin Jourde, Michael Fahey, Paul Kleihues & Hiroko Ohgaki

  2. Cancer Registry, Canton of Zurich, 8091, Zurich, Switzerland

    Danielle Schüler & Nicole M. Probst-Hensch

  3. Department of Neurosurgery, College of Medicine, Little Rock, Arkansas, 72205, USA

    M. Gazi Yasargil

  4. Department of Neurosurgery, University Hospital Zurich, 8091, Zurich, Switzerland

    Yasuhiro Yonekawa

  5. Department of Radiology, University Hospital Zurich, 8091, Zurich, Switzerland

    Urs M. Lütolf

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  1. Yoshikazu Okamoto
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Correspondence to Hiroko Ohgaki.

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Okamoto, Y., Di Patre, PL., Burkhard, C. et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol 108, 49–56 (2004). https://doi.org/10.1007/s00401-004-0861-z

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  • DOI: https://doi.org/10.1007/s00401-004-0861-z

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