Test ID: EGFR
EGFR Gene, Mutation Analysis, 29 Mutation Panel, Tumor

Identifying non-small cell lung cancers that may respond to epidermal growth factor receptor-tyrosine kinase inhibitor therapies

When this test is ordered, slide review will always be performed at an additional charge.

• Informed Consent for Genetic Testing

Polymerase Chain Reaction (PCR) Analysis

(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

Pathology report must accompany specimen in order for testing to be performed.

Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.

Preferred:

Specimen Type: Tissue

Container/Tube: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block.

Acceptable:

Specimen Type: Tissue

Container/Tube: Slides

Specimen Volume: 1 stained and 5 unstained

Collection Instructions: Submit 1 slide stained with hematoxylin-and-eosin and 5 unstained, non-baked slides with 5-micron thick sections of the tumor tissue.

Lung cancer is the leading cause of cancer-related deaths in the world. Non-small cell lung cancer (NSCLC) represents 70% to 85% of all lung cancer diagnoses. Small molecular agents that target the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) protein are approved for the treatment of locally advanced or metastatic NSCLC as a second- or third-line regimen. Subsequently, randomized trials have suggested that targeted agents alone or combined with chemotherapy may be beneficial in maintenance and first-line settings. Because the combination of targeted therapy and standard chemotherapy leads to an increase in toxicity and cost, strategies that help to identify the individuals most likely to benefit from targeted therapies are desirable.

EGFR is a growth factor receptor that is activated by the binding of specific ligands, resulting in activation of the RAS/MAPK pathway. Activation of this pathway induces a signaling cascade ultimately leading to cell proliferation. Dysregulation of the RAS/MAPK pathway is a key factor in tumor progression for many solid tumors. Targeted therapies directed to tumors harboring activating mutations within the EGFR tyrosine kinase domain (exons 18-21) have demonstrated some success in treating a subset of patients with NSCLC by preventing ATP-binding at the active site. Gefitinib and erlotinib have been approved by the FDA for use in treating patients with NSCLC who previously failed to respond to the traditional platinum-based doublet chemotherapy. These 2 drugs have also recently been shown to increase progression-free and overall survival in patients who receive EGFR-tyrosine kinase inhibitor therapy as a first-line therapy for the treatment of NSCLC.

Agents such as gefitinib and erlotinib, which prevent ATP binding to EGFR kinase, do not appear to have any meaningful inhibitor activity on tumors that demonstrate the presence of the specific drug-resistant EGFR mutation T790M. Therefore, current data suggest that the efficacy of EGFR-targeted therapies in NSCLC is confined to patients with tumors demonstrating the presence of EGFR- activating mutations such as L858R, L861Q, G719A/S/C, S768I or small deletions within exon 19 and the absence of the drug-resistant mutation T790M. As a result, the mutation status of EGFR can be a useful marker by which patients are selected for EGFR-targeted therapy.

An interpretive report will be provided.

An interpretive report will be provided.

A negative (wild type) result does not rule out the presence of a mutation that may be present but below the limits of detection for this assay (approximately 10%).  

A negative (wild type) result does not rule out the presence of other activating mutations in the EGFR gene.

The predictive value of epidermal growth factor receptor (EGFR) testing applies to EGFR-TKI therapies, not to other therapeutic agents.

Not all patients that have activating EGFR mutations detected by this assay respond to EGFR-TKI therapies.

Rare polymorphisms exist that could lead to false-negative or false-positive results.

See references.

1. Sharma SV, Bell DW, Settleman J, Haber DA: Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007;7(3):169-181

2. Gao G, Ren S, Li A, et al: Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: a meta-analysis from six phase III randomized controlled trials. Int J Cancer 2011;131(5):E822-829

3. Mok TS: Personalized medicine in lung cancer: what we need to know. Nat Rev Clin Oncol 2011;8:661-668

A PCR-based assay employing Scorpions real-time PCR and allele-specific PCR technologies is used to test for 29 mutations within exons 18 through 21 of the EGFR gene:

A pathology review and macro dissection to enrich for tumor cells is performed prior to DNA extraction.(Package insert: EGFR RGQ PCR Kit, Qiagen, Valencia, CA, 2011)

Monday through Friday; 10 am

81235-EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants (eg, exon 19 LREA deletion, L858R, T790M, G719A, G719S, L861Q)

88381-Microdissection, manual