title: p53 mutations versus EGF receptor expression in giant cell glioblastomas.
abstract: Recent studies have shown that there are distinct genetic pathways leading to the most malignant astrocytic neoplasm, the glioblastoma. Primary (de novo) glioblastomas are characterized by amplification/overexpression of the EGF receptor (EGFR) and, less frequently, of the MDM2 gene. Another pathway, operative in the progression of low-grade or anaplastic astrocytomas to secondary glioblastomas, is characterized by the frequent occurrence of p53 mutations. In this study, we assessed p53 mutations and EGFR expression in the giant cell glioblastoma. This rare variant is characterized by unusually large, multinucleated giant cells, but tends to be more confined and has been reported to carry a somewhat more favorable prognosis. We analyzed biopsies from 16 patients (mean age at clinical manifestation, 40 years). DNA sequencing revealed that 12 of 16 (75%) giant cell glioblastomas contained a p53 mutation. In 7 patients with two or more surgical interventions, the p53 mutation was already detected in the first biopsy. Focal EGFR overexpression, including multinucleated giant cells, was observed immunohistochemically in 9 of 16 (56%) tumors. However, most tumor areas lacked immunoreactivity, indicating that EGFR overexpression does not play a significant role in the evolution of this glioblastoma variant. These results suggest that giant cell glioblastomas develop de novo with a short preoperative history (mean, 47 +/- 40 days), but contain genetic alterations similar to those observed in secondary glioblastomas.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Peraud
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: K H
authors.initials: KH
authors.lastname: Plate
authors.forename: Y
authors.initials: Y
authors.lastname: Yonekawa
authors.forename: P
authors.initials: P
authors.lastname: Kleihues
authors.forename: H
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002648:Child; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors