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Test ID: FLCA    
Lung Cancer, ALK (2p23) Rearrangement, FISH, Tissue

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

Identifying patients with late-stage, non-small cell lung cancers who may benefit from treatment with the drug Xalkori

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

Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung carcinoma (NSCLC) accounts for 75% to 80% of all lung cancers with an overall 5-year survival rate of 10% to 15%. Standard chemotherapy regimens have had marginal success in improving clinical outcomes. Targeted treatments may be used as novel molecular changes are identified.


Rearrangements of the ALK locus are found in a subset of lung carcinomas and their identification may guide important therapeutic decisions for the management of these tumors. The fusion of EML4 (echinoderm microtubule-associated protein-like 4) gene with the ALK (anaplastic large cell lymphoma kinase) gene results from an inversion of chromosome band 2p23. The ALK-EML4 rearrangement has been identified in 3% to 5% of NSCLC with the majority in adenocarcinoma and younger male patients who were light or nonsmokers. Lung cancers harboring ALK rearrangements are resistant to epidermal growth factor receptor tyrosine kinase inhibitors, but may be highly sensitive to ALK inhibitors, like Xalkori (crizotinib).The drug Xalkori works by blocking certain kinases, including those produced by the abnormal ALK gene. Clinical studies have demonstrated that Xalkori treatment of patients with tumors exhibiting ALK rearrangements can halt tumor progression or result in tumor regression.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretative report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A positive result (ALK rearrangement identified) is detected when the percent of cells with an abnormality exceeds the normal cutoff for the ALK probe set. A positive result suggests rearrangement of the ALK locus and a tumor that may be responsive to ALK inhibitor therapy. A negative result suggests no rearrangement of the ALK gene region at 2p23.


A specimen is considered positive if >50% demonstrate a signal pattern consistent with an ALK rearrangement and considered negative if <10% of cells are positive. If the results are equivocal (>10% and <50%), an additional 50 cells are scored and would be considered positive if >15% of cells exhibit a signal pattern consistent with an ALK rearrangement and negative if <15% of cells exhibit an ALK rearrangement.

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

This test is intended to be used for therapeutic purposes in pulmonary carcinoma. This FISH assay does not rule out other chromosome abnormalities        

While results may indicate the likely response to ALK inhibitor therapy, selection of treatment remains a clinical decision

Supportive Data

Initial validation studies were performed on 40 paraffin-embedded lung tissue specimen including 15 non-small cell lung carcinoma and 25 noncancerous lung tissue control specimens using the FDA-approved protocol. Additional verification studies were performed on 19 samples and demonstrated concordant results between the FDA method and a laboratory-developed protocol.

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

1. Soda M, Choi YL, Enomoto M, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-566

2. Boland JM, Erdogan S, Vasmatzis G, et al: Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas. Hum Pathol 2009;40:1152-1158

3. Shaw AT, Yeap BY, Mino-Kenudson M, et al: Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 2009;27:4247-4253

4. Shaw AT, Yeap BY, Solomon BJ, et al: Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 2011;12:1004-1012

5. Koivunen JP, Mermel C, Zejnullahu K, et al: EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res 2008;13:4275-4283

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test