Epidermal growth factor receptor gene amplification and expression in disseminated pediatric low-grade gliomas

Uri Tabori, Shlomit Rienstein, Yaara Dromi, Leonor Leider-Trejo, Shlomo Constantini, Yoav Burstein, Rina Dvir, Ninette Amariglio, Amos Toren, Gideon Rechavi, Shai Izraeli, Ayala Aviram

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Object. Pediatric low-grade gliomas (LGGs) are the largest group of central nervous system neoplasms in children. Although these tumors are generally benign, 5 to 10% of patients with pediatric LGGs present with leptomeningeal dissemination. The genetic and biological nature of these tumors is poorly understood. The authors looked for certain molecular abnormalities that may differentiate disseminated gliomas from the other pediatric LGGs. Methods. Comparative genomic hybridization (CGH) was applied to 18 pediatric LGGs. Six cases featuring disseminated pediatric LGGs were compared with 12 control cases involving nondisseminated pediatric LGGs. Fluorescence in situ hybridization (FISH) analysis and immunohistochemical analysis were used to highlight further specific genetic targets. The CGH revealed multiple chromosomal abnormalities in five of six cases with disseminated gliomas and in six of 12 control cases. No correlation was found between the number of chromosomal abnormalities and dissemination status. Amplification of chromosome 7 was noted in four of six cases with disseminated gliomas as opposed to one of 12 control cases (p = 0.02). The FISH analysis revealed epidermal growth factor receptor (EGFR) amplification in one case negative to chromosome 7 amplification by CGH, raising the amplification cases to five of six (p = 0.0038). Immunohistochemical analysis for EGFR was positive in six of six cases and in two of 12 control cases (p = 0.0015). At the end of a mean follow-up period of 7.2 years, all patients with disseminated gliomas are alive with variable but slow disease progression. Conclusions. The high rate of EGFR gene amplification and protein expression in disseminated pediatric LGGs is intriguing and may have implications for our understanding of the role of EGFR in glioma genesis. Targeted therapies may be available for these children. Larger-scale studies are needed to establish further these findings.

Original languageEnglish
Pages (from-to)357-361
Number of pages5
JournalJournal of Neurosurgery
Volume103 PEDIATRICS
Issue numberSUPPL. 4
DOIs
StatePublished - Oct 2005

Keywords

  • Dissemination
  • Epidermal growth factor receptor
  • Low-grade glioma
  • Pediatric neurosurgery

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