Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods?

Over-expression of the epidermal growth factor receptor (EGFR) in tumours is associated with aggressive disease and poor clinical prognosis. In theory, the EGFR status of a tumour provides an indication of the likelihood of response to EGFR-targeted therapy. However, the clinical data do not support a relationship between EGFR expression and response to EGFR-targeted therapies cetuximab, gefitinib and erlotinib. Recently, patients who appear to lack EGFR expression have been shown to respond to cetuximab. Possible causes for this paradox include false negative results due to a lack of sensitivity in the detection system, heterogeneity of EGFR expression within the tumour and specific mutations that mediate response to the tyrosine kinase inhibitors. Immunohistochemistry is the most reliable assay for EGFR expression but its interpretation is confounded by the lack of non-standard techniques. Other approaches for measuring EGFR expression can be considered at best exploratory at this point. Further work is needed to identify how EGFR contributes to carcinogenic and metastatic processes. As tumours that appear to be EGFR negative can respond to cetuximab, there is some doubt as to the usefulness of immunohistochemistry as a screen to select patients for treatment. Histopathology will continue to be essential for unravelling the role of this enigmatic molecule and refining its status as a legitimate target in cancer therapy.