Test Id : RETF

This test includes a charge for the probe application, analysis, and professional interpretation of results for one probe set (2 individual fluorescence in situ hybridization probes). No analysis charges will be incurred if an insufficient number of representative cells are available for analysis.

Appropriate ancillary probes may be performed at consultant 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.

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

Confirmation testing for the presence of a possible RET 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.

Advise Express Mail or equivalent if not on courier service.

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.

1. Patient name

2. Block number - must be on all blocks, slides, and paperwork

3. Date of collection

4. 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.

Submit only 1 of the following specimens:

Preferred

Specimen Type: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tumor tissue block. Blocks prepared with alternative fixation methods will be attempted but are less favorable for successful results by fluorescence in situ hybridization testing; provide fixation method used.

Additional Information:

1. Paraffin-embedded specimens can be from any anatomic location (skin, soft tissue, lymph node, etc).

2. Bone specimens that have been decalcified will be attempted for testing, but the success rate is approximately 50%.

Acceptable

Specimen Type: Tissue slides

Slides: 1 Hematoxylin and eosin stained and 4 unstained

Collection Instructions: Submit 4 consecutive unstained, positively charged, unbaked slides with 5 micron-thick sections of the tumor tissue and 1 slide stained with hematoxylin and eosin.

If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.

Slides: 1 Hematoxylin and eosin stained and 2 unstained

Identifying RET gene rearrangements in patients with late-stage, lung adenocarcinomas that are negative for epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements

Fluorescence in situ hybridization (FISH) testing for RET allows for the detection of most RET rearrangements.  Therefore, RET FISH testing is useful for identifying tumors that may be sensitive to directed therapy. RET FISH testing may also support the diagnosis of certain salivary gland, cutaneous and other tumors in the proper clinica and pathologic context

This test includes a charge for the probe application, analysis, and professional interpretation of results for one probe set (2 individual fluorescence in situ hybridization probes). No analysis charges will be incurred if an insufficient number of representative cells are available for analysis.

Appropriate ancillary probes may be performed at consultant 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.

Chromosomal rearrangements of the RET proto-oncogene at chromosome 10q11 resulting in fusion of the RET gene with various partner genes has been identified as a recurrent abnormality in several tumor types including but not limited to some non-small cell carcinomas of the lung, thyroid carcinomas, salivary gland carcinomas, and soft tissue tumors

Clinical data has shown that tumors harboring RET fusions may be sensitive to directed inhibitor therapy.

An interpretive report will be provided.

RET will be clinically interpreted as positive or negative.

A result is considered positive when the percent of cells with separation of the RET fluorescence in situ hybridization (FISH) probes exceeds the normal cutoff for the RET FISH probe set.

A positive result is consistent with rearrangement of the RET gene and likely reflects RET fusion with a partner gene. The significance of this FISH result is dependent on additional clinical and pathologic features.

A positive result may support a certain diagnosis in a particular clinical and pathologic context.

A positive result suggests that the tumor may be sensitive to directed kinase inhibitors. While results may indicate the potential response to directed tyrosine kinase inhibitors, selection of treatment remains a clinical decision.

A negative result does not exclude the presence of a RET fusion or exclude the possible sensitivity to targeted therapy.

This test is not approved by the U.S. Food and Drug Administration, and it is best used as an adjunct to existing clinical and pathologic information.

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

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

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%.

FISH 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 signals are observed post-hybridization, the case will be released indicating a lack of FISH results.

1. Wang R, Hu H, Pan Y, et al. RET fusions define a unique molecular and clinicopathologic subtype of non–small-cell lung cancer. J Clin Oncol. 2012;30(35):4352-9

2. Weinreb I, Bishop JA, Chiosea SI, et al. RET gene rearrangements in intraductal carcinomas of salivary gland. Am J Surg Pathol. 2018;42(4):442

3. Lee MY, Ku BM, Kim HS, et al. Genetic alterations and their clinical implications in high-recurrence risk papillary thyroid cancer. Cancer Res Treat. 2017;49(4):906-14

4. Drilon A, Oxnard GR, Tan DS, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med. 2020;383(9):813-24

5. Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med. 2020;383(9):825-35

6. Aldea M, Marinello A, Duruisseaux M, et al. RET-MAP: An international multicenter study on clinicobiologic features and treatment response in patients with lung cancer harboring a RET fusion. J Thorac Oncol. 2023;18(5):576-586

7. Antonescu CR, Suurmeijer AJ, Zhang L, et al. Molecular characterization of inflammatory myofibroblastic tumors with frequent ALK and ROS1 gene fusions and rare novel RET rearrangement. Am J Surg Pathol. 2015;(7)39:957-967

The test is performed using a laboratory-developed RET (10q11) dual-color, break-apart strategy probe (BAP). 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 independently analyze 50 interphase nuclei (100 total) with the results expressed as the percent of abnormal nuclei.(Unpublished Mayo method)

Monday through Friday

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• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

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.

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)