Cellular and tumoural heterogeneity of EGFR gene amplification in human malignant gliomas.

Abstract

It has been demonstrated that the epidermal growth factor receptor (EGFR) gene, the normal human counterpart of the viral erb-B oncogene is amplified and overexpressed in over 50% of human malignant gliomas (HMGs). In the present study, analysis of the immunohistological staining characteristics of 57 HMGs using an anti-EGFR monoclonal antibody (mab) showed positive staining in 65% of the tumours with large cellular and regional differences in staining pattern and intensity. Screening a smaller number of HMGs with molecular hybridization techniques revealed 10/21 glioblastomas (48%) amplified for the gene; of 11 glioblastomas studied by Northern blot hybridization, 7 tumours with gene amplification showed RNA overexpression, the remaining 4 without amplification did not. Regional differences in DNA levels were observed by Southern blot in 2 tumours: in one particular case, amplification and overexpression were found to be localized to one half of a single HMG, the other half showing neither EFGR gene amplification nor overexpression.