title: Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas.
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.
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372, Lyon Cedex 08, France.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Pier-Luigi
authors.initials: PL
authors.lastname: Di Patre
authors.forename: Christoph
authors.initials: C
authors.lastname: Burkhard
authors.forename: Sonja
authors.initials: S
authors.lastname: Horstmann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jourde
authors.forename: Michael
authors.initials: M
authors.lastname: Fahey
authors.forename: Danielle
authors.initials: D
authors.lastname: Schüler
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Probst-Hensch
authors.forename: M Gazi
authors.initials: MG
authors.lastname: Yasargil
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: Urs M
authors.initials: UM
authors.lastname: Lütolf
authors.forename: Paul
authors.initials: P
authors.lastname: Kleihues
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000367:Age Factors; D000368:Aged; D001254:Astrocytoma / Q000453:epidemiology / Q000235:genetics / Q000401:mortality / Q000601:surgery; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D019656:Loss of Heterozygosity / Q000502:physiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D019635:Neurosurgical Procedures / Q000379:methods; D009837:Oligodendroglioma / Q000453:epidemiology / Q000235:genetics / Q000401:mortality / Q000601:surgery; D012189:Retrospective Studies; D012737:Sex Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53