P53 MUTATIONS VERSUS EGF RECEPTOR EXPRESSION IN GIANT-CELL GLIOBLASTOMAS

Recent studies have shown that there are distinct genetic pathways lea ding to the most malignant astrocytic neoplasm, the glioblastoma. Prim ary (de novo) glioblastomas are characterized by amplification/overexp ression of the EGF receptor (EGFR) and, less frequently, of the MDM2 g ene. Another pathway, operative in the progression of low-grade or ana plastic astrocytomas to secondary glioblastomas, is characterized by t he frequent occurrence of p53 mutations. In this study, we assessed p5 3 mutations and EGFR expression in the giant cell glioblastoma. This r are 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 analysed biopsies from 16 patien ts (mean age at clinical manifestation, 40 years). DNA sequencing reve aled that 12 of 16 (75%) giant cell glioblastomas contained a p53 muta tion. In 7 patients with two or more surgical interventions, the p53 m utation was already detected in the first biopsy. Focal EGFR overexpre ssion, including multinucleated giant cells, was observed immunohistoc hemically in 9 of 16 (56%) tumors. However, most tumor areas lacked im munoreactivity, indicating that EGFR overexpression does not play a si gnificant role in the evolution of this glioblastoma variant. These re sults suggest that giant cell glioblastomas develop de novo with a sho rt preoperative history (mean, 47 +/- 40 days), but contain genetic al terations similar to those observed in secondary glioblastomas.