FISH for Non-Small Cell Lung Cancer:
ALK and ROS1
A Rapid, Comprehensive Test for Therapy Selection
NeoGenomics offers single-test and panel options for ROS1 and FDA-approved ALK testing. These tests:
Identify patients who may respond to XALKORI® (crizotinib)
Approximately 3-5% of non-small cell lung carcinomas (NSCLC) have a rearrangement of the ALK gene, resulting in fusion between ALK and another gene, ALK activation, impaired apoptosis, and abnormal cell proliferation. Patients with such tumors have been shown to respond to the ALK kinase inhibitor XALKORI® (crizotinib).1 NeoGenomics uses the FDA-approved companion diagnostic, the Vysis ALK Break Apart FISH Probe Kit, to identify patients for this therapy.2
ROS1 gene rearrangements, detected in 1-2% of NSCLC, share with ALK rearrangements a similar biological defect, predominant histology (adenocarcinoma), and patient demographic profile (younger age, non-smoker, increased frequency of Asian ethnicity).3-5 ROS1 and ALK rearrangements appear to be mutually exclusive.3-5 Pre-clinical studies and early clinical reports show some ROS1-rearranged tumors are sensitive to crizotinib, with comparable objective response rates in ALK+ and ROS1+ patients.3,5-7
ALK rearrangement testing by FISH and EGFR molecular testing are recommended for recurrent or metastatic cases with histological subtypes of adenocarcinoma, large cell carcinoma, or NSCLC NOS (not otherwise specified), and for squamous cell carcinoma in never-smokers or when biopsy specimens are small.8 NCCN Guidelines also specify that ROS1-positive patients may be treated with crizotinib.8
Are more comprehensive than other test methods
FISH is better-suited than molecular testing to detect the spectrum of variants of ALK and ROS1 rearrangements. The ALK gene has more than 20 known rearrangement partner genes,9 with 15 variants of the most common EML4-ALK fusion. ROS1 has seven partners described so far in NSCLC.10 While molecular assays must be designed to individual and unique fusions, FISH detection encompasses all described and as-yet undescribed rearrangements.11
IHC-based selection of ALK or ROS1 positive patients for therapy has not been clinically validated.
Shown are representative cases of ALK FISH with results negative for the arrangement (top left, with two intact, fused ALK loci) and positive (bottom left, with one ALK locus intact and one split apart). Like the ALK test, NeoGenomics’ ROS1 FISH also uses a dual-color break-apart probe which produces single green, red, and yellow or fusion signals in rearranged cells.
|Stand-alone ALK using the FDA-approved Vysis ALK Break Apart FISH Probe Kit
|Stand-alone ROS1 Consider adding this to previously-tested ALK negative tumors.
|ALK concurrent with ROS1
|ALK reflex to ROS1
||Tech-only clients should use test add-on process instead.|
|ALK, add-on ROS1 if ALK is negative
Specimen Requirements: Please submit the following for ROS1 testing alone or in combination with the NeoTYPE™ Lung Tumor Profile, ALK FISH, and/or EGFR molecular testing.
- Paraffin block with 10% neutral buffered formalin-fixed paraffin-embedded (FFPE) lung tissue plus one H&E slide cut at 4-5 microns (circle area of invasive tumor for tech-only). H&E slide is required.
- If ordering FISH with molecular testing, please note preferred testing sequence if limited tumor is present.
Turnaround Time: 3-5 days
- Kwak EL et al. New Engl J Med. 2010;363(18):1693-1703.
- Vysis ALK Break Apart FISH Probe Kit package insert. Vysis ALK United States website. Accessed 12-31-2012.
- Bergethon K, Shaw AT, Ignatius Ou S, et al. J Clin Oncol. 2012;30(8):863-870.
- Takeuchi K, Soda M, Togashi Y, et al. Nature Med. 2012;18(3):378-381.
- Davies KD, Le AT, Theodoro MF, et al. Clin Cancer Res. 2012;18(17):4570-4579.
- Shaw AT, Camidge DR, Engelman JA, et al. J Clin Oncol. 2012;30 (suppl): abstract 7508.
- Bang YJ. Arch Pathol Lab Med. 2012;136:1201-1204.
- NCCN Guidelines, Non-Small Cell Lung Cancer, version 1.2013. National Comprehensive Cancer Network website. Accessed 12-31-2012.
- ALK page. Atlas of Genetics and Cytogenetics in Oncology and Haematology. Accessed 12-31-2012; last updated 2-2010.
- Stumpfova M, Janne PA. Clin Cancer Res. 2012;18(16):4222-4224.
- Sasaki T et al. Eur J Cancer. 2010;46:1773-1780.