_em_EGFR__em_ Mutation Testing
Also known as:Epidermal Growth Factor Receptor Mutation Analysis; HER-1; erbB-1
Formal name:Epidermal Growth Factor Receptor
Related tests:Tumor Markers, Genetic Tests for Targeted Cancer Therapy, KRAS Mutation, ALK Mutation
Were you looking instead for Estimated Glomerular Filtration Rate, also known as eGFR? If so, see the article on eGFR.
Why Get Tested?
To detect an EGFR gene mutation in tumor tissue to help guide treatment of non-small cell lung cancer
When to Get Tested?
When you have been diagnosed with non-small cell lung cancer and your health practitioner is considering treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib
A sample of cancer tissue obtained during a biopsy
Test Preparation Needed?
How is it used?
EGFR mutation testing is used primarily to help guide treatment and determine whether someone with non-small cell lung cancer (NSCLC) may benefit from targeted therapy such as with the tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. This testing detects the presence of specific activating mutations in the EGFR gene in the DNA of cells in tumor tissue.
EGFR-activating mutations can lead to uncontrolled growth of cancer cells. TKIs block the action of EGFR, which inhibits cell growth. If a person's lung cancer has an EGFR mutation, then a TKI may be effective in treating his or her cancer.
An EGFR mutation test may be ordered by itself or as part of a series of tests that also includes KRAS and/or ALK mutation testing. Each of these tests may be used to help determine whether a person's lung cancer will respond to targeted therapy and which type will likely be of most benefit.
When is it ordered?
EGFR mutation testing is ordered when an individual has been diagnosed with non-small cell lung cancer, especially adenocarcinoma, and the person is a candidate for treatment with an EGFR inhibitor.
Currently, if EGFR mutation testing is performed as part of a series of tests, KRAS mutation testing is usually done first. If the tumor is negative for KRAS, then EGFR mutation testing may be done, and if that is negative, then a test for ALK mutation may be performed.
What does the test result mean?
If KRAS mutation testing is performed and indicates that the tumor lacks a KRAS mutation, then the affected person is likely to respond to an anti-EGFR drug therapy (tyrosine kinase inhibitor, TKI). If the tumor has a KRAS mutation, then it is unlikely to harbor an EGFR mutation or respond to anti-EGFR drug therapy. (In non-small cell lung cancer, EGFR and KRAS mutations are mutually exclusive–the tumor can have one or the other but not both.)
If EGFR mutation testing indicates that an EGFR-activating mutation is present in cancer tissue, then the affected individual is likely to respond to therapy that targets EGFR. If the tumor is negative for an EGFR mutation, then the person is not likely to respond to a tyrosine kinase inhibitor. ALK mutation testing may then used to determine whether the person's tumor would be likely to respond to an ALK kinase inhibitor.
A person could have a negative test result if the tumor tissue sample is insufficient and/or when there are insufficient cancer cells present that contain the mutation. Additionally, there may be EGFR mutations present that are not detected by this testing.
Is there anything else I should know?
If a patient has already been exposed to a tyrosine kinase inhibitor and is showing signs of resistance to the medication, the health practitioner may order tests that look for specific EGFR resistance mutations.
In addition to non-small cell lung cancer, there is an increased amount of EGFR present in other types of cancer. Some examples include colon cancer, glioblastoma (a type of brain cancer), and cancers of the head and neck, breast, and pancreas. This can be due to amplification and over-expression of the receptor that leads to excessive signaling for growth. Tumors that have increased EGFR protein tend to grow more aggressively, are more likely to metastasize, and are more resistant to standard chemotherapies.
EGFR blocking agents are also routinely used for treatment of metastatic colon cancer and are used with some head and neck cancers.
The utility of EGFR inhibitors and their correlation with EGFR mutations in different types of cancers has yet to be fully established. The role of testing for certain EGFR gene mutations and the mutations' affect on a person's responsiveness to treatment continues to be explored.
EGFR mutation testing is not available in every laboratory. If a health practitioner sends a sample to a reference laboratory, the results may take a few weeks before they are available.
What is being tested?
EGFR is a short name for the epidermal growth factor receptor gene. This test detects mutations in the EGFR gene in cancer tissue. This information is useful in guiding treatment of non-small cell lung cancer.
The EGFR gene codes for a specialized protein called a receptor located on the surface of cells. Receptors recognize and bind to other substances, and the binding typically has a specific effect on the cells.
EGFR is one of a group of receptors called receptor tyrosine kinases that help regulate cell growth, division, survival, and death. This regulation is a very complex process involving the activation of a series of signals along various pathways. Receptor tyrosine kinases like EGFR transmit signals from the surface of the cell to within the cell.
In normal cells, the binding of epidermal growth factor to its receptor on the cell surface is an important signal that promotes cell proliferation. Certain mutations called "activating mutations" in the EGFR gene can result in excessive signaling for growth and uncontrolled proliferation of cancer cells.
Treatment that targets EGFR is a valuable molecular approach in cancer therapy. Examples of EGFR-targeted therapy include drugs such as gefitonib and erlotinib, which are small molecules called tyrosine kinase inhibitors (TKIs) that enter cancer cells and impede signaling.
These drugs have been shown to be useful in treating non-small cell lung cancer (NSCLC). Studies have shown that targeted therapy with these TKIs will only work in a subset of NSCLC with specific activating mutations in the EGFR gene. If an activating mutation is present, as detected with an EGFR mutation test, then the drugs directed against EGFR are much more likely to be effective and the patient should benefit from targeted therapy.
How is the sample collected for testing?
A sample of cancer tissue is obtained by performing a biopsy.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
- Can I have my blood tested for EGFR mutations?
No. It is not the genetics of the person being evaluated but the genes of the tumor, so a sample of the tumor obtained with a biopsy is used for testing.
- What is the difference between EGFR, also known as Her-1, and Her-2/neu?
EGFR and Her-2/neu are both members of the same family of cell membrane receptors. When either EGFR or Her-2/neu is significantly increased in a cancer, it indicates a more aggressive tumor and a poorer patient prognosis. The primary differences between EGFR and Her-2/neu are that they are ordered to help evaluate different types of cancer and that the drugs that have been developed to target them are specific for that particular receptor, EGFR or Her-2/neu. Her-2/neu is used for evaluating breast cancer.
- Are there other types of testing performed to evaluate EGFR in tumors?
There is a test available that looks at the genetic level for gene amplification; it evaluates the number of copies of the gene present. Sometimes tests for EGFR gene amplification are used to determine the likely course (prognosis) of cancer of the head and neck. Tumors with amplified EGFR tend to grow more aggressively, are more likely to metastasize, and are more resistant to standard chemotherapies. People with these tumors tend to have a poorer outcome.
© 2017 American Association for Clinical Chemistry, republished from Lab Tests Online.*
Descriptions of clinical laboratory tests were originally prepared for use on Lab Tests Online, an award-winning patient education website on clinical laboratory testing. Lab Tests Online is produced by the American Association for Clinical Chemistry (AACC), a global scientific and medical professional organization dedicated to clinical laboratory science and its application to healthcare. The Lab Tests Online website is developed in collaboration with other laboratory professional societies and is funded in part through corporate sponsorships.