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HelpTest Code LCAF Lung Cancer, ALK (2p23) Rearrangement, FISH, Tissue
Useful For
Identifying ALK gene rearrangements irrespective of the ALK fusion partner gene
Identifying patients with non-small cell lung carcinoma who may benefit from treatment with directed tyrosine kinase inhibitors
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| _PBCT | Probe, +2 | No, (Bill Only) | No |
| _PADD | Probe, +1 | No, (Bill Only) | No |
| _PB02 | Probe, +2 | No, (Bill Only) | No |
| _PB03 | Probe, +3 | No, (Bill Only) | No |
| _IL25 | Interphases, <25 | No, (Bill Only) | No |
| _I099 | Interphases, 25-99 | No, (Bill Only) | No |
| _I300 | Interphases, >=100 | No, (Bill Only) | No |
Testing Algorithm
This test includes a charge for probe application, analysis, and professional interpretation of results for one probe set (2 individual fluorescence in situ hybridization probes). Analysis charges are based on the number of cells analyzed per probe. No analysis charges apply if there are insufficient representative cells for evaluation.
Appropriate ancillary probes may be performed at the consultant's discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.
Method Name
Fluorescence In Situ Hybridization (FISH)
Reporting Name
ALK (2p23), Lung Cancer, FISH, TsSpecimen Type
TissueOrdering Guidance
This test does not include a pathology consultation. If a pathology consultation is requested, order PATHC / Pathology Consultation, and appropriate testing will be added at the discretion of the pathologist and performed at an additional charge.
Multiple oncology (cancer) gene panels are also available. For more information see Hematology, Oncology, and Hereditary Test Selection Guide
Additional Testing Requirements
Confirmation testing for the presence of a possible ALK fusion transcript by next-generation sequencing to resolve atypical or unbalanced fluorescence in situ hybridization results is available, order MCLNR / MayoComplete Lung Rearrangements, Rapid Test, Tumor.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
1. A pathology report is required for testing to be performed. If not provided, appropriate testing and/or interpretation may be compromised or delayed. Acceptable pathology reports include working drafts, preliminary pathology, or surgical pathology reports.
2. The following information must be included in the report provided:
-Patient name
-Block number - must be on all blocks, slides, and paperwork
-Collection date
-Tissue source
3. A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
Specimen Required
Submit only 1 of the following specimens:
Preferred:
Specimen Type: Tissue block (fresh tissue is not acceptable)
Collection Instructions:
1. Submit a formalin-fixed, paraffin-embedded tumor tissue block.
2. Blocks prepared with alternative fixation methods (eg, Prefer, Bouin's) will be attempted but are less favorable for successful results. Provide fixation method used.
Additional Information:
1. Paraffin-embedded specimens can be from any anatomic location (skin, soft tissue, lymph node, etc).
2. Decalcified paraffin-embedded specimens will have testing attempted; however, the success rate is approximately 50%. Testing may be canceled if sufficient tumor tissue is not present.
3. Submitted fresh tissue specimens will be canceled upon receipt. If only fresh tissue is available, embed in paraffin prior to sending.
Acceptable:
Specimen Type: Tissue slides
Slides: 1 Hematoxylin and eosin-stained and 4 unstained
Collection Instructions: Submit 1 slide stained with hematoxylin and eosin and 4 consecutive unstained, positively charged, unbaked slides with 5-micron-thick sections of the tumor tissue.
Additional Information: Broken or cracked unstained slides will be rejected. Stained slides that were broken and repaired (ie, double mounted) at the client site will not be rejected, as, in most cases, they can still be reviewed under the microscope. However, due to the double mounting, digital scanning cannot be performed.
Specimen Minimum Volume
Slides: 1 Hematoxylin and eosin-stained and 2 unstained
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Tissue | Ambient (preferred) | |
| Refrigerated | ||
Reject Due To
| Broken or cracked unstained slides | Reject |
| Broken or cracked stained slides that cannot be repaired | Reject |
Clinical Information
Rearrangements of the ALK (anaplastic lymphoma kinase) gene are found in approximately 3% to 5% of non-small cell lung carcinomas with the majority in adenocarcinoma and younger female patients who were light or nonsmokers. Clinical studies have shown that lung cancers harboring ALK rearrangements are resistant to epidermal growth factor receptor tyrosine kinase inhibitors but may be highly sensitive to directed tyrosine kinase inhibitors.
Reference Values
An interpretative report will be provided.
Interpretation
ALK will be clinically interpreted as positive or negative.
Interpretive criteria for the ALK fluorescence in situ hybridization (FISH) assays are provided by the manufacturer, Abbott Molecular.
A specimen is considered positive if greater than 50% demonstrate a signal pattern consistent with an ALK rearrangement and considered negative if less than 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 greater than 15% of cells exhibit a signal pattern consistent with an ALK rearrangement and negative if less than 15% of cells exhibit an ALK rearrangement.
A positive result is consistent with rearrangement of the ALK gene and likely reflects ALK fusion with a partner gene. A positive result suggests that the tumor may be responsive to directed therapy in the proper clinical and pathologic context. While results may indicate the potential response to directed tyrosine kinase inhibitors, selection of treatment remains a clinical decision.
A negative result suggests that an ALK gene rearrangement is not present but does not completely exclude the presence of an ALK gene rearrangement or exclude the possible sensitivity to targeted therapy.
A negative result does not exclude the presence of a neoplastic disorder.
Cautions
This test is intended to be used for therapeutic purposes in pulmonary carcinoma.
While results may indicate the likely response to ALK inhibitor therapy, selection of treatment remains a clinical decision.
This fluorescence in situ hybridization (FISH) assay does not rule out other chromosome abnormalities.
Fixatives other than formalin (eg, Prefer, Bouin's) may not be successful for FISH assays. Non-formalin fixed specimens will not be rejected.
Paraffin-embedded tissues that have been decalcified may not be successful for FISH analysis. The success rate of FISH studies on decalcified tissue is approximately 50%, but FISH will be attempted if sufficient tumor is present for analysis.
Fluorescence in situ hybridization studies will be attempted if sufficient tumor is present for analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing if insufficient tissue/tumor is available for testing.
If no FISH signal or a lack of sufficient tumor tissue is observed post-hybridization, the case will be reported indicating a lack of FISH results.
Clinical Reference
1. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693-1703
2. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385-2394
3. Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017; 377(9):829-838
4. Sholl LM, Weremowicz S, Gray SW, et al. Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas. J Thorac Oncol. 2013;8(3):322-328
5. Horn L, Wang Z, Wu G, et al. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: A Randomized Clinical Trial. JAMA Oncol. 2021;7(11):1617-1625
Method Description
The test is performed using a US Food and Drug Administration-approved ALK (2p23) dual-color, break-apart strategy fluorescence in situ hybridization probe set (Abbott Molecular). Paraffin-embedded tissue samples 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-stained slide as a reference, target areas are etched with a diamond-tipped engraving tool on the back of the unstained slide to be assayed. The probe set is hybridized to the appropriate target areas, and 2 technologists each analyze 25 interphase nuclei (50 total) with the results expressed as the percent of abnormal nuclei.(Unpublished Mayo method)
Day(s) Performed
Monday through Friday
Report Available
7 to 9 daysSpecimen Retention Time
Slides and H and E used for analysis are retained by the laboratory in accordance with regulatory requirements. Client provided paraffin blocks and extra unstained slides will be returned after testing is complete.Performing Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
88271x2, 88291-DNA probe, each (first probe set), Interpretation and report
88271x2-DNA probe, each; each additional probe set (if appropriate)
88271x1-DNA probe, each; coverage for sets containing 3 probes (if appropriate)
88271x2-DNA probe, each; coverage for sets containing 4 probes (if appropriate)
88271x3-DNA probe, each; coverage for sets containing 5 probes (if appropriate)
88274 w/modifier 52-Interphase in situ hybridization, <25 cells, each probe set (if appropriate)
88274-Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| LCAF | ALK (2p23), Lung Cancer, FISH, Ts | 78205-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 52115 | Result Summary | 50397-9 |
| 52117 | Interpretation | 78210-2 |
| 54580 | Result | 62356-1 |
| CG740 | Reason for Referral | 42349-1 |
| 52118 | Specimen | 31208-2 |
| 52119 | Source | 31208-2 |
| 52120 | Tissue ID | 80398-1 |
| 52121 | Method | 85069-3 |
| 55023 | Additional Information | 48767-8 |
| 53835 | Disclaimer | 62364-5 |
| 52122 | Released By | 18771-6 |
NY State Approved
YesDisease States
- Non-small cell lung cancer
Forms
If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.