Current and ex-smokers with primary lung adenocarcinoma should be tested for EGFR mutation

Introduction: The Aberdeen Molecular Genetics Laboratory began testing lung cancers in June 2009. To date 1,178 samples have been tested from Scotland, England and Northern Ireland. The majority of tumours tested are adenocarcinomas (>97%). This is due to case selection as there are a low number, if any, EGFR mutations in squamous cell carcinoma. In addition, only EGFR testing in nonsmall cell lung carcinoma is currently relevant from the non-trial prescribing perspective. Methods: Samples have histopathology assessment in Aberdeen followed by macro-dissection to enrich for tumour where appropriate/possible, prior to DNA extraction and molecular testing. Tumour samples are tested in parallel for mutations in EGFR (exons 18 21), KRAS (codons 12, 13, 61) and BRAF (codon 600) genes using a combination of methods including Sanger sequencing, fragment length analysis, and cobas. Results: Overall mutation detection rates are 16%, 29.8%, 3.3% for EGFR, KRAS and BRAF respectively. Stratification of patients according to smoking status revealed EGFR mutations in approximately 44% of non-smokers, 7% of current smokers, and 10% of ex-smokers. This finding is independent of gender. KRAS mutation was detected in 11% non-smokers, 29% of current smokers and 40% of ex-smokers. Further subdivision of the exsmoker patient group according to number of years stopped revealed an EGFR positive rate of 18% in ex>15 years and 6% of ex<15 years. The most common KRAS mutation detected was c.34G>T; p.Gly12Cys. This was found in 44% and 39% of KRAS positive never and current smoking groups respectively. 2.2% of samples completely failed to produce an EGFR result. The combined fail/partial fail rate for EGFR ranged from 4.4% to 20.7% according to referral centre. Conclusion: EGFR mutations are found in a significant proportion of Adenocarcinoma NSCLC tumours arising in current and ex smokers. It is therefore important that these patient groups are not excluded from testing.