The Tumor Biomarker Series: EGFR

Epidermal growth factor receptor (EGFR) is the most frequently amplified oncogene in astrocytic tumors (>40% or GBMs and 5-10% of anaplastic astrocytomas). EGFR is far more often amplified in de novo GBMs as compared to secondary GBMs. About one-half of those GBMs with EGFR amplification also have specific EGFR mutations (the vIII mutant), which produce a truncated receptor with constitutive activity. Both EGFR amplification and EGFRvIII mutant are mutually exclusive with IDH mutations. So, what is the utility of EGFR testing? First, astrocytomas with EGFR amplification tend to be of higher grade. So if, for example, the diagnostician is vacillating between a WHO grade II and a WHO grade III tumor, positive EGFR amplification status would favor the latter. Secondly, EGFR amplification can also help distinguish between a small cell GBM (which would potentially harbor the amplification) from anaplastic oligodendrogliomas (which do not exhibit the amplification).