CID ALK FISH Testing
Rearrangement involving the ALK gene on 2p23 with the EML4 gene on 2p21 is present in approximately 5% of lung adenocarcinomas. Lung tumors with ALK rearrangement have been shown to respond to ALK kinase inhibitors (1). In addition, in 70-80% of ALK-positive anaplastic large cell lymphomas (ALCL), ALK is paired with Nucleophosmin (NPM) on 5q35, and with a variety of other genes in the remaining. ALK rearrangements have also been described in other tumors including inflammatory myofibroblastic tumors, neural tumors, and in some subtypes of breast cancer and of rhabdomyosarcomas. Almost invariably, ALK translocations result in chimeric proteins containing a 5’-end partner fused to the ALK tyrosine kinase domain at the 3’-end. Deregulated ALK activity has an oncogenic effect, and targeted therapies against this kinase are currently being analyzed to treat cancers harboring rearrangements in the ALK locus.
Fluorescence in situ hybridization (FISH) using formalin-fixed paraffin-embedded specimens has been shown to be an effective method for determining presence of these translocations. Briefly, 5-micron sections of formalin-fixed paraffin-embedded tumor material are prepared and an H&E section is reviewed to select regions for hybridization that contain a majority of tumor cells. An ALK break-apart probe (Kreatech ALK Breakapart FISH Proximal Green and Distal Red probes) is hybridized, and used to calculate the number of cells out of 50 scored containing a rearrangement. An ALK rearrangement is reported if more than 15% of cells show split signals and is confirmed with the ALK break-apart probe (Vysis LSI ALK (2p23) Dual Color, Break Apart Rearrangement Probe).
- Specimen Type: Tissue
- Specimen Requirements: H&E and four unstained 5-micron slides
- Turn Around Time: Two weeks