Lung Cancer, ROS1 (6q22) Rearrangement, FISH, Tissue
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Identifying ROS1 gene rearrangements in patients with late-stage, lung adenocarcinomas that are negative for EGFR mutations and ALK rearrangements
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
This test does not include a pathology consult. If a pathology consultation is requested, 70012 Pathology Consultation should be ordered and the appropriate FISH test will be ordered and performed at an additional charge.
This test may be ordered independently or in addition to FLCA/60619 Lung Cancer, ALK (2p23), FISH, Tissue and FRET/62456 Lung Cancer, RET (10q11), FISH, Tissue. If ordered in addition to the other tests, this test would only be performed if no ALK rearrangement is identified. If an ALK rearrangement was identified, testing for a ROS1 rearrangement would be cancelled.
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Lung Cancer, ROS1 (6q22), FISH, Ts
Non-small cell lung cancer
Non-small cell lung cancer
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 reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.
Advise Express Mail or equivalent if not on courier service.
Forms: If not ordering electronically, please submit a Hematopathology/Molecular Oncology request Form (Supply T241) with the specimen.
Submit only 1 of the following specimens:
Specimen Type: Tissue block
Collection Instructions: Submit formalin-fixed, paraffin-embedded tumor tissue block.
Specimen Type: Slides
Collection Instructions: Submit 2 consecutive, unstained 5 micron-thick sections placed on positively-charged slides and 1 hematoxylin and eosin-stained slide.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
1 unstained slide
Note: No specimen should be rejected. If specimen not received at appropriate temperature, include note to laboratory. If questions, contact laboratory.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Lung cancer is the leading cause of cancer mortality in developed countries. The discovery of a variety of genetic alterations in non-small-cell lung cancer (NSCLC) has enabled the use of targeted therapy such as the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, for NSCLC with ALK rearrangements and EGFR mutations, respectively.
The c-ros oncogene 1 (ROS1), originally described in glioblastomas, has been identified as a potential relevant therapeutic target in lung adenocarcinoma. Crizotinib has shown in vitro activity and early evidence of clinical activity in ROS1-rearranged tumors.
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 interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the probe set.
A positive result suggests rearrangement of the ROS1 locus and a tumor that may be responsive to ALK-inhibitor therapy. A negative result suggests no rearrangement of the ROS1 gene region at 6q22.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA, and it is best used as an adjunct to existing clinical and pathologic information.
Fixatives other than formalin (eg, Prefer, Bouin) may not be successful for FISH assays. Although FISH testing will not be rejected due to nonformalin fixation, results may be compromised.
Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing.
The probe set was independently validated in a blinded study on 20 paraffin-embedded lung adenocarcinoma tissue samples and 25 noncancerous control samples. Rearrangements of ROS1 were verified in samples previously identified with a ROS1 rearrangement using reverse-transcriptase-PCR testing methods. The normal controls were used to generate a normal cut-off for this assay.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Suehara Y, Arcila M, Wang L, et al: Identification of KIF5B-RET and GOPC-ROS1 fusions in lung adenocarcinomas through a comprehensive mRNA-based screen for tyrosine kinase fusions. Clin Cancer Res 2012;18(24):6599-6608
2. Takeuchi K, Soda M, Togashi Y, et al: RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18(3):378-381
3. Bergethon K, Shaw AT, Ou SH, et al: ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol 2012;30(8):863-870
4. Chin LP, Soo RA, Soong R, Ou SH: Targeting ROS1 with anaplastic lymphoma kinase inhibitors: a promising therapeutic strategy for a newly defined molecular subset of non-small-cell lung cancer. J Thorac Oncol 2012;7(11):1625-1630
Method Description Describes how the test is performed and provides a method-specific reference
Rearrangements of ROS1 are detected using a laboratory developed dual-color break-apart probe (BAP) strategy probe set. Paraffin-embedded tissues are cut at 5 microns and mounted on positively charged glass slides. The selection of tissue and the identification of target areas on the hematoxylin and eosin (H and E)-stained slide are performed by a pathologist. Using the H and E slide as a reference, target areas are etched with a diamond-tipped etcher on the back of the unstained slide to be assayed. The probe is hybridized to the appropriate target areas and 2 technologists each analyze 50 interphase nuclei (100 total) per probe set 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.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
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, each
88275-Interphase in situ hybridization, 100-300 cells
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|
|CG648||Reason For Referral||42349-1|