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Published on: August 11, 2017
EGFR tyrosine kinase mutation testing in the treatment of non-small-cell lung cancer
S Kamel-Reid1, G Chong, D N Ionescu
1Department of Pathology, The University Health Network, Toronto, ON.
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.
Insights
Standardized methods for detecting epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are feasible for routine clinical screening. These tests reliably identify key EGFR mutations in tumor samples, enabling targeted therapies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Non-small-cell lung cancer (NSCLC) with activating mutations in epidermal growth factor receptor (EGFR) tyrosine kinase are sensitive to targeted therapies.
- Assessing EGFR mutation status is crucial for treatment selection, but standardized methods for routine screening are lacking.
- This study aimed to validate methods for detecting EGFR mutations in exons 19 and 21.
Purpose of the Study:
- To validate the feasibility and reliability of existing methods for detecting EGFR mutations in exons 19 and 21.
- To assess the performance of these methods in molecular laboratories within specialized Canadian cancer centers.
- To determine if routine screening for EGFR mutations in NSCLC is viable in clinical practice.
Main Methods:
- Methods were initially optimized using cell lines with known EGFR mutations.
- A validation phase involved testing anonymized patient tumor samples.
- Molecular laboratories in five specialized Canadian cancer centers participated in the study.
Main Results:
- Optimized methods demonstrated high specificity (100%) and sensitivity (≥1%) for detecting EGFR mutations in cell line DNA.
- Excellent concordance (approximately 87%) was observed between laboratories when analyzing patient samples.
- Discordant results were generally associated with samples containing limited tumor material.
Conclusions:
- Currently available methods can reliably detect EGFR exon 19 and 21 mutations in tumor samples.
- Sufficient tumor material is necessary for accurate mutation detection.
- Routine screening for EGFR mutations in NSCLC is feasible in clinical practice, supporting targeted treatment strategies.
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