NON-SMALL CELL LUNG CANCER

ANALYSIS OF THE TYROSINE KINASE DOMAIN OF THE EGFR GENE TO PREDICT RESPONSE TO EGFR TYROSINE KINASE INHIBITORS

Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers (Herbst et al. 2008 New Engl J Med 359:1367-1380).  The epidermal growth factor receptor (EGFR) signaling pathway is implicated in tumour cell growth, local invasion, angiogenesis, metastasis, protein translation and cell metabolism.  Activating somatic variants in the tyrosine kinase domain (exons 18-21) of the EGFR gene have been identified in 10-20% of NSCLC tumours, the majority of which are adenocarcinomas (Lynch et al. 2004 NEJM 350: 2129-2139).  These variants are associated with sensitivity to tyrosine kinase inhibitors (TKIs) such as gefitinib (Iressa) and erlotinib (Tarceva).   (Lynch et al. 2004 NEJM 350: 2129-2139, Paez et al. 2004 Science 304:1497-1500, Pao et al. 2004 PNAS 101:13306-13311, Zhou et al. 2011 The Lancet Oncol 12:735).  The most common disease-causing variants are the exon 19 deletions and the p.Leu858Arg (p.L858R) variant in exon 21.  Together these variants account for approximately 85% of all EGFR variants.

For information regarding ALK testing: http://www.exeterlaboratory.com/cellular-pathology/anaplastic-lymphoma-kinase-alk-testing-in-lung-cancer/

Useful links: http://www.egfr-mutation.com/

Recommended clinical referral criteria: Chemo-naive patients with NSCLC, suitable for treatment with tyrosine kinase inhibitors.

Reporting time: 5-10 working days from sample receipt.

Laboratory contact: Christopher Bowles 01392 408249 (Christopher.Bowles@nhs.net)

Histopathology contact: Dr Manish Powari 01392 402998 (Manish.Powari@nhs.net)

The laboratory participates in the United Kingdom National External Quality Assessment Service (UK NEQAS) scheme for the molecular genetic analysis of EGFR in non-small cell lung cancer and the European Molecular Genetics Quality Network (EMQN) sequencing scheme.