EGFR tyrosine kinase mutation testing in the treatment of non-small-cell lung cancer.

Kamel-Reid S, Chong G, Ionescu DN, Magliocco AM, Spatz A, Tsao M, Weng X, Young S, Zhang T, Soulieres D.

Source

Department of Pathology, The University Health Network, Toronto, ON.

Abstract

BACKGROUND:

Non-small-cell lung cancer (nsclc) tumours with activating mutations of the epidermal growth factor receptor (efgr) tyrosine kinase are highly sensitized to the effects of oral tyrosine kinase inhibitors such as gefitinib and erlotinib, suggesting the possibility of targeted treatment of nsclc based on EFGR mutation status. However, no standardized method exists for assessing the EGFR mutation status of tumours. Also, it is not known if available methods are feasible for routine screening. To address that question, we conducted a validation study of methods used for detecting EGFR mutations in exons 19 and 21 at molecular laboratories located in five specialized Canadian cancer centres.

METHODS:

The screening methods were first optimized using cell lines harbouring the mutations in question. A validation phase using anonymized patient samples followed.

RESULTS:

The methods used at the sites were highly specific and sensitive in detecting both mutations in cell-line dna (specificity of 100% and sensitivity of at least 1% across all centres). In the validation phase, we observed excellent concordance between the laboratories for detecting mutations in the patient samples. Concordant results were obtained in 26 of 30 samples (approximately 87%). In general, the samples for which results were discordant were also less optimal, containing small amounts of tumour.

CONCLUSIONS:

Our results suggest that currently available methods are capable of reliably detecting exon 19 and exon 21 mutations of EFGR in tumour samples (provided that sufficient tumour material is available) and that routine screening for those mutations is feasible in clinical practice.