Epidermal growth factor receptor in glioblastomas: correlation between gene copy number and protein expression

Abstract

Epidermal growth factor receptor is a transmembrane receptor involved in oncogenesis, including the development of glioblastoma. We studied the prognostic significance of epidermal growth factor receptor amplification as determined by fluorescence in situ hybridization, quantitative polymerase chain reaction, and protein expression by immunohistochemistry. Ninety-nine patients exhibiting glioblastoma were included. Immunohistochemistry was performed on microarray blocks with clone 25, which recognizes both epidermal growth factor receptor wild type and vIII, and scored using a semiquantitative approach. Quantitative polymerase chain reaction and fluorescence in situ hybridization techniques were performed on frozen section: 29.3% of cases had a high epidermal growth factor receptor immunohistochemistry score (score >/=200); and of these cases, 96.5% had gene amplification by fluorescence in situ hybridization and quantitative polymerase chain reaction. Conversely, of cases with a low immunohistochemistry score, 72.9% had normal karyotype or polysomy 7 by fluorescence in situ hybridization technique; but around 25% had gene amplification by fluorescence in situ hybridization and quantitative polymerase chain reaction. In the case of protein overexpression, quantitative polymerase chain reaction and fluorescence in situ hybridization could be avoided in first intention because their positive predictive value for amplification is 97%. In multivariate analysis, there was a trend toward an association between shorter overall survival time and epidermal growth factor receptor amplification as determined by fluorescence in situ hybridization analysis. However, cases with an immunohistochemistry score less 200 require further testing by fluorescence in situ hybridization or quantitative polymerase chain reaction.