EGFR Mutation Testing in Non-Small Cell Lung Cancer

Non-small cell lung cancer [NSCLC] is a major cause of cancer related deaths in the world. In a significant proportion of NSCLC cases, the Epidermal Growth Factor Receptor [EGFR] is over-expressed prompting the development of anti-EGFR therapies. Clinical studies of EGFR tyrosine kinase inhibitors [TKIs] demonstrated an overall response rate of 10% in NSCLC with higher response rates in females, never smokers, adenocarcinoma histology and East Asians. Mutations in exons 18-21 of the EGFR gene appear to be the most important molecular predictors of response to TKIs with response rates of >60% reported in most studies. Consequently screening NSCLC patients for tumours harbouring EGFR mutations will assist in selecting patients for TKI therapy. The gold standard for detecting EGFR mutations has been direct DNA sequencing however the sensitivity of this molecular technique is limited by the amount of tumour DNA is time and resource consuming. Recently several highly sensitive techniques have been developed to detect EGFR mutant DNA in different biological samples. In this review we aim to provide an overview of the clinical relevance of screening for EGFR mutations in NSCLC and recent molecular tests that have been developed for this purpose to allow the reader to critically evaluate the various methodologies that are available.