Download PDF: EGFR Mutation Testing in lung cancer
Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer. While first-line treatment often involves platinum-based combination chemotherapy, targeted treatment is also available for some types of advanced NSCLC. Twenty percent of NSCLC tumours harbour an activating mutation in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) – which plays a role in cellular tumour growth and proliferation – and approximately 85% of patients with these mutations respond to targeted treatment with EGFR TK inhibitors (TKIs) such as gefitinib, erlotinib and afatinib. Testing for mutations in EGFR is therefore an important step in the treatment-decision pathway.
Historically, the standard for EGFR mutation testing involved direct sequencing of DNA extracted from samples of tumour tissue (gathered during biopsy or resection). Direct sequencing, however, has low sensitivity (i.e., only detects mutations when sufficient levels of mutant DNA are present), and can be complex and time-consuming. A number of alternative methods for mutation testing with improved sensitivity and turnaround times have been developed over recent years. Types of method currently available include:
- ‘Targeted’ methods that detect specific, known mutations with commercially available test kits enabling sensitive, rapid and robust analysis,
- ‘Screening’ methods (subsequent to sample micro dissection) that detect all mutations, including more rare, uncommon variants (see Table 1 for advantages and disadvantages of both method types).
Table 1: Comparison of EGFR Mutation Testing Methods in Tumour Tissue Samples
| Screening methods (samples screened for all EGFR mutations, known and novel variants) | Targeted methods (samples analysed for known EGFR mutations only) | |
| Advantages |
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| Disadvantages |
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EGFR, epidermal growth factor receptor.
- In addition, alternative sources of tumour material, in particular cytology samples, can be successfully used to determine EGFR mutation status provided that sensitive testing methods are employed. Evidence published to date suggests that mutation detection rates with cytology samples are comparable with those achieved with traditional tissue samples obtained by biopsy or resection. As cytology samples can be obtained by less invasive procedures including fine needle aspirate and pleural effusion, their use may be more appropriate in advanced disease where tumour biopsy samples is not always possible due to co-morbidities or other reasons.
Choice of testing methods
In practice, the choice of testing method should be based primarily on the nature of the sample to be tested including tumour content (particularly for cytology material), the testing laboratory’s expertise and available equipment, and whether detection of known activating EGFR mutations only or all possible mutations is required (see algorithm).
Key Messages
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Reference: 1- Gillian Ellison, et al. EGFR Mutation Testing in Lung Cancer. A Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66(2):79-89.