FISH for RET Gene Rearrangements

RET (10q11) Gene Rearrangement

Clinical Significance:

Recently established guidelines from the American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and/or the American Society of Clinical Oncology (ASCP) recommend testing for all newly diagnosed non-small cell, non-squamous lung carcinomas or such metastatic lung carcinomas that have not had a primary resection available for testing.  RET (10q11) gene fusions can be found in 1-2% of NSCLC, more commonly in adenocarcinomas of never or light smokers, whose tumors lack EGFR and KRAS mutations.  Patients with RET gene rearrangements, characteristically due to KIF5B-RET, CCDC6-RET, NCOA4-RET, and TRIM33-RET fusion, rendering the tumors sensitive to RET inhibitors such as cabozantinib (while resistant to EGFR tyrosine kinase inhibitor therapies). 

https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf

Specimen Requirements and Collection:

Formalin fixed tissue containing a sufficient amount of tumor (generally at least several mm of tumor tissue submitted in the tissue block). 

Methodology:

Fluorescent in-situ hybridization (FISH)

Forms:

Molecular pathology requisition form

Transport:

Send formalin-fixed, paraffin-embedded (FFPE) tissue and cell block containing tumor at room temperature.  Also acceptable 10-unstained, 4-5 micron slides with 1 post H&E.  Please include a surgical pathology report

Unacceptable specimen:

Specimens fixed in alternative fixatives or metal fixatives (ex. B-plus).  Decalcified specimens.

Reference Range:

RET gene rearrangement present = positive result

RET gene rearrangement not detected = negative result

CPT codes:

88377

Test reported:

Results are reported within 7-10 days