Test ID: FLCA
Lung Cancer, ALK (2p23) Rearrangement, FISH, Tissue
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
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
Method Name A short description of the method used to perform the test
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Non small cell lung cancer
Non-small cell lung cancer
NSCLC
ALK
2p23
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Provide a pathology report with each specimen. The laboratory will not reject specimens that arrive without this information but will hold the specimen until a pathology report is received.
Specimen Type: Formalin-fixed, paraffin-embedded unknown primary tumor cancer tissue block
Forms: If not ordering electronically, submit a Cytogenetics Hematologic Disorders Request Form (Supply T607) with the specimen.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Tissue | Ambient (preferred) | |
| Refrigerated | ||
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. Recent studies have demonstrated that 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. This FISH assay is a FDA-approved companion diagnostic test for the Xalkori, which the FDA recently approved to treat certain patients with late-stage (locally advanced or metastatic), non-small cell lung cancers that harbor anaplastic lymphoma kinase (ALK) gene rearrangements. It can be used to identify patients who will benefit from Xalkori therapy.
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
While results may indicate the likely response to ALK inhibitor therapy, selection of treatment remains a clinical decision
Supportive Data
Blinded validation studies were performed utilizing FISH on 40 paraffin-embedded lung tissue specimen including 15 non-small cell lung carcinoma and 25 noncancerous lung tissue control specimens. Specimens were previously tested using a lab-developed FISH protocol and results were concordant with the FDA-approved probe kit. The ALK gene rearrangement was not detected in any of the control specimens.
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
Method Description Describes how the test is performed and provides a method-specific reference
The test uses an FDA-approved ALK dual-color, break-apart rearrangement probe kitset. The ALK probe consists of 2 probes that flank the ALK gene region at 2p23 (Abbott Molecular). Five micron sections of formalin-fixed, paraffin-embedded tissue specimens are cut and mounted on positively-charged glass slides. The selection of tissue and the identification of target areas on the hematoxylin and eosin-stained slide are performed by a pathologist. The probe set is hybridized to the appropriate target areas and 2 technologists analyze 25 interphase nuclei each (50 total). Results are reported based on the guidelines include with the probe kit and package insert with the results expressed as the percent abnormal nuclei. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
88271 x 2-DNA Probe
88274-Interphase in situ hybridization
88291-Interpretation and report
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 51141 | Specimen | N/A |
| 51142 | Specimen ID | N/A |
| 51143 | Source | N/A |
| 51144 | Order Date | N/A |
| CG583 | Reason For Referral | N/A |
| 51146 | Method | N/A |
| 51147 | Result | N/A |
| 51148 | Interpretation | N/A |
| 51149 | Amendment | N/A |
| 51150 | Reviewed By | N/A |
| 51151 | Release Date | N/A |
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