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To detect a KRAS gene mutation in tumor tissue in order to guide cancer therapy and to evaluate prognosis
When you have colon cancer that has spread (metastatic) or non-small cell lung cancer
A sample of tumor tissue obtained through a biopsy procedure or sometimes collected during surgery
This test detects specific mutations in the KRAS gene in the DNA of cancer cells and tissue. The presence of these mutations may indicate that certain drugs will not be effective in treating the cancer.
KRAS is a short name for the gene Kirsten rat sarcoma viral oncogene homolog. It is one of a group of genes involved in a pathway called the epidermal growth factor receptor (EGFR) pathway. This complex signaling pathway involves numerous components that relay signals from outside of the cell to within the cell to help regulate cell growth, division, survival and death.
In many normal cells, binding of epidermal growth factor (EGF) to its receptor (EGFR) on the surface of the cell is an important signal for cell growth and division. Other signals in the pathway involve a class of proteins called tyrosine kinase (TK) enzymes and a protein produced by the KRAS gene. Normally, the components of the pathway interact in the regulation of cell growth and division and do not individually stimulate cell proliferation.
However, in some cancers, EGFR becomes active even in the absence of EGF, leading to uncontrolled cell growth and division. Drugs that inhibit EGFR or tyrosine kinase enzymes are often helpful for treating such cancers. Some of these cancers, though, have a mutation in the KRAS gene that produces an abnormal K-Ras protein. The abnormal protein is always active and can stimulate cell growth even in the absence of signals from EGFR or other tyrosine kindase proteins. In such cancers, drugs that inhibit EGFR or tyrosine kinases will not be effective.
KRAS is mutated in 15% to 20% of human cancers, mostly in pancreatic cancer, colon cancer and lung cancers as well as leukemias. Approximately 30% to 40% of colon cancers and 15% to 30% of lung cancers have KRAS mutations. Currently, drugs that target EGFR are used to treat colon cancer and non-small cell lung cancer. KRAS mutation testing is used to determine whether these drugs will be effective in treating these cancers.
There are several different methods of testing for KRAS mutations, but all of them involve evaluating the KRAS gene in tumor tissue.
This test detects the presence of the most common KRAS gene mutations in the DNA of cells in tumor tissue in order to help guide cancer treatment. KRAS mutation analysis is ordered primarily to determine if your metastatic colon cancer or non-small cell lung cancer is likely to respond to standard therapy, an anti-EGFR drug therapy. Tumors with the KRAS mutation do not respond to anti-EGFR therapy.
If your tumor is negative for the most common KRAS mutation, tests for other less common mutations not detected by the current test may be used to help predict therapeutic responses.
A KRAS mutation test is usually ordered when you have been diagnosed with metastatic colon cancer or non-small cell lung cancer. It may be performed at any time prior to the start of treatment.
If tissue from your cancer contains a KRAS mutation, then you will not benefit from EGFR targeted therapies. The presence of a KRAS mutation also indicates a likely poorer prognosis, although the presence of a specific mutation cannot predict how severe or aggressive the cancer will be.
A negative result on the KRAS test indicates that your cancer may respond to anti-EGFR therapy, but the lack of a KRAS mutation as determined by the KRAS test does not ensure this. A negative test could occur when the tumor tissue sample is insufficient or when some of the cancer cells in the tumor contain the mutation and others do not. Additionally, there may be KRAS mutations that are not detected by some tests because of their particular location in the DNA. Other factors may also lead to cancer that is resistant to anti-EGFR drugs.
Guidelines from both the American Society of Clinical Oncology and the National Comprehensive Cancer Network have recommended KRAS mutation testing prior to anti-EGFR therapy.
Current anti-EGFR drug therapies include:
Testing is not generally indicated unless a person has colon cancer or non-small cell lung cancer.
It is possible, since KRAS mutations are found in other cancers. This is a focus for medical researchers, but it may be some time before the usefulness of the testing and therapy in other cancers is determined. For example, whether KRAS mutations are associated with less efficient EGFR-targeted therapy in pancreatic cancer patients remains controversial and requires further investigation.
This is not usually necessary but might occur if your health practitioner thought that the first sample tested might have been insufficient. In some cases, a health care provider may order a KRAS test that detects a mutation in another part of the DNA or another more rare KRAS mutation. Sometimes metastatic tumors may be not be accessible or have limited tissue for testing. In these cases, a sample (if available) from your primary cancer may be obtained for testing. Frequently, if the primary tumor has a KRAS mutation, so will the metastatic tumor.
It may be available in some larger laboratories, but must often it will be sent to a reference laboratory. Depending on the laboratory, it may take a few days or weeks for results to be available.
Some medical laboratories can perform KRAS mutation testing on tumor tissue as well as bone marrow and blood. However, the research that evaluated the role of KRAS mutations in treatment response was based solely on tumor testing. Therefore, the preferred sample for KRAS testing is tumor tissue.
Sources Used in Current Review
Current review performed by Hui Li, PhD, DABCC, FACB, FCACB, Clinical Chemist, Dynacare and the Editorial Review Board.
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Chiramel J et. al. (2017 April 26). Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis. Available online at http://www.mdpi.com/1422-0067/18/5/909. Accessed January 2019.
Shen et al. (2017 March 07). Diagnostic and prognostic value of blood samples for KRAS mutation identification in lung cancer: a meta-analysis. Available online at http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path=15972&pubmed-linkout=1. Accessed January 2019.
Sobani et. al. (2016 Oct 10). Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056326/pdf/WJCO-7-340.pdf. Accessed January 2019.
Wang JP et. al. (2015 Jul 20). Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial. Available online at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627242/pdf/oncotarget-06-18162.pdf. Accessed January 2019.
Quest Diagnostics [On-line information]. KRAS Mutation Analysis. Available online at https://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=16510. Accessed January 2019.
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