Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas

J Neuropathol Exp Neurol. 2005 Jun;64(6):479-89. doi: 10.1093/jnen/64.6.479.

Abstract

Published data on prognostic and predictive factors in patients with gliomas are largely based on clinical trials and hospital-based studies. This review summarizes data on incidence rates, survival, and genetic alterations from population-based studies of astrocytic and oligodendrogliomas that were carried out in the Canton of Zurich, Switzerland (approximately 1.16 million inhabitants). A total of 987 cases were diagnosed between 1980 and 1994 and patients were followed up at least until 1999. While survival rates for pilocytic astrocytomas were excellent (96% at 10 years), the prognosis of diffusely infiltrating gliomas was poorer, with median survival times (MST) of 5.6 years for low-grade astrocytoma WHO grade II, 1.6 years for anaplastic astrocytoma grade III, and 0.4 years for glioblastoma. For oligodendrogliomas the MSTwas 11.6 years for grade II and 3.5 years for grade III. TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but infrequent (13%) in oligodendrogliomas. LOH 1p/19q typically occurred in tumors without TP53 mutations and were most frequent in oligodendrogliomas (69%), followed by oligoastrocytomas (45%), but were rare in fibrillary astrocytomas (7%) and absent in gemistocytic astrocytomas. Glioblastomas were most frequent (3.55 cases per 100,000 persons per year) adjusted to the European Standard Population, amounting to 69% of total incident cases. Observed survival rates were 42.4% at 6 months, 17.7% at one year, and 3.3% at 2 years. For all age groups, survival was inversely correlated with age, ranging from an MST of 8.8 months (<50 years) to 1.6 months (>80 years). In glioblastomas, LOH 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations, and was the only alteration associated with shorter survival of glioblastoma patients. Primary (de novo) glioblastomas prevailed (95%), while secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hot-spot codons 248 and 273, while in primary glioblastomas, mutations were more evenly distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas, suggesting that the acquisition of TP53 mutations in these glioblastoma subtypes may occur through different mechanisms.

Publication types

  • Review

MeSH terms

  • Age Distribution
  • Astrocytoma* / epidemiology
  • Astrocytoma* / genetics
  • Astrocytoma* / mortality
  • Astrocytoma* / secondary
  • Brain Neoplasms* / epidemiology
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / mortality
  • Chromosomes, Human, Pair 10
  • Disease Progression
  • Humans
  • Incidence
  • Loss of Heterozygosity*
  • Mutation
  • Oligodendroglioma* / epidemiology
  • Oligodendroglioma* / genetics
  • Oligodendroglioma* / mortality
  • Predictive Value of Tests
  • Recurrence
  • Sex Factors
  • Survival Rate
  • Switzerland / epidemiology
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53