title: The definition of primary and secondary glioblastoma.
abstract: Glioblastoma is the most frequent and malignant brain tumor. The vast majority of glioblastomas (~90%) develop rapidly de novo in elderly patients, without clinical or histologic evidence of a less malignant precursor lesion (primary glioblastomas). Secondary glioblastomas progress from low-grade diffuse astrocytoma or anaplastic astrocytoma. They manifest in younger patients, have a lesser degree of necrosis, are preferentially located in the frontal lobe, and carry a significantly better prognosis. Histologically, primary and secondary glioblastomas are largely indistinguishable, but they differ in their genetic and epigenetic profiles. Decisive genetic signposts of secondary glioblastoma are IDH1 mutations, which are absent in primary glioblastomas and which are associated with a hypermethylation phenotype. IDH1 mutations are the earliest detectable genetic alteration in precursor low-grade diffuse astrocytomas and in oligodendrogliomas, indicating that these tumors are derived from neural precursor cells that differ from those of primary glioblastomas. In this review, we summarize epidemiologic, clinical, histopathologic, genetic, and expression features of primary and secondary glioblastomas and the biologic consequences of IDH1 mutations. We conclude that this genetic alteration is a definitive diagnostic molecular marker of secondary glioblastomas and more reliable and objective than clinical criteria. Despite a similar histologic appearance, primary and secondary glioblastomas are distinct tumor entities that originate from different precursor cells and may require different therapeutic approaches.
authors.affiliation: Molecular Pathology Section, International Agency for Research on Cancer, Lyon, France. ohgaki@iarc.fr
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
authors.forename: Paul
authors.initials: P
authors.lastname: Kleihues
mesh_terms: D001254:Astrocytoma / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology
chemical_list: D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human