EGFRmutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples

Abstract

Aims: Activating mutations in the gene encoding epidermal growth factor receptor (EGFR) can confer sensitivity to EGFR tyrosine kinase inhibitors such as gefitinib in patients with advanced non-small-cell lung cancer. Testing for mutations inEGFRis therefore an important step in the treatment-decision pathway. We reviewed reported methods forEGFRmutation testing in patients with lung cancer, initially focusing on studies involving standard tumour tissue samples. We also evaluated data on the use of cytology samples in order to determine their suitability forEGFRmutation analysis.Methods: We searched the MEDLINE database for studies reporting onEGFRmutation testing methods in patients with lung cancer.Results: Various methods have been investigated as potential alternatives to the historical standard forEGFRmutation testing, direct DNA sequencing. Many of these are targeted methods that specifically detect the most commonEGFRmutations. The development of targeted mutation testing methods and commercially available test kits has enabled sensitive, rapid and robust analysis of clinical samples. The use of screening methods, subsequent to sample micro dissection, has also ensured that identification of more rare, uncommon mutations is now feasible. Cytology samples including fine needle aspirate and pleural effusion can be used successfully to determineEGFRmutation status provided that sensitive testing methods are employed.Conclusions: Several different testing methods offer a more sensitive alternative to direct sequencing for the detection of commonEGFRmutations. Evidence published to date suggests cytology samples are viable alternatives for mutation testing when tumour tissue samples are not available.