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Interpretive Handbook

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Test 50256 :
KRAS Mutation Analysis, 7 Mutation Panel, Other (Non-Colorectal)

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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. Randomized trials have suggested that targeted agents alone or combined with chemotherapy may be beneficial. Because the addition of targeted therapy may lead to an increase in toxicity and cost, strategies that help to identify the individuals most likely to benefit from targeted therapies are desirable. Monoclonal antibodies against epidermal growth factor receptor (EGFR) represent a new area of targeted therapy for such patients. However, studies have shown that not all individuals with NSCLC respond to these EGFR-targeted molecules.

 

EGFR is a growth factor receptor that is activated by the binding of specific ligands (epiregulin and amphiregulin), 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. Targeted therapies directed to EGFR, which inhibit activation of the RAS/MAPK pathway, have demonstrated some success in treating a subset of patients with NSCLC.

 

In NSCLC, one of the most frequently reported alterations in the EGFR-signaling pathway is the presence of a mutation in the proto-oncogene KRAS. KRAS is recruited by ligand-bound (active) EGFR to initiate the signaling cascade induced by the RAS/MAPK pathway. Because mutant KRAS constitutively activates the RAS/MAPK pathway downstream of EGFR, agents that prevent ligand-binding to EGFR do not appear to have any meaningful inhibitor activity on cell proliferation in the presence of mutant KRAS. Current data suggest that the efficacy of EGFR-targeted therapies in NSCLC is confined to patients with tumors lacking KRAS mutations. As a result, the mutation status of KRAS can be a useful marker by which patients are selected for EGFR-targeted therapy.

 

At this time, this test is for noncolorectal tumors. Please refer to KRAS7 / KRAS Mutation Analysis, 7 Mutation Panel, Colorectal for KRAS testing in colorectal tumors.  

Useful For Suggests clinical disorders or settings where the test may be helpful

Prognostic marker for cancer patients with noncolorectal tumors treated with epidermal growth factor receptor-targeted therapies

Interpretation Provides information to assist in interpretation of the test results

An interpretative report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Not all patients who have wild-type KRAS respond to epidermal growth factor receptor (EGFR)-targeted therapies.

 

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

 

Test results should be interpreted in context of clinical findings, tumor sampling, and other laboratory data. If results obtained do not match other clinical or laboratory findings, please contact the laboratory for possible interpretation. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Eberhard DA, Johnson BE, Amler LC, et al: Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005;23(25):5900-5909

2. Ladanyi M, Pao W: Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol 2008;21 Suppl 2:S16-S22

3. Lam DC: Clinical testing for Molecular targets for personalized treatment in lung cancer. Respirology 2012. doi: 10.1111/j.1440-1843.2012.02261.x. (Epub ahead of print)


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