Detecting ALK+ NSCLC

ALK gene rearrangements are present in approximately 5% of patients with NSCLC1

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) and CAP clinical guidelines recommend that patients with metastatic NSCLC be routinely tested for ALK+ disease.2,3

ALK may be detected by using a variety of methods.4-6

  • Fluorescence in situ hybridization (FISH)4
    • Uses fluorescently labeled DNA probes that bind to and localize specific regions in the tumor nuclei to detect ALK rearrangements and amplification
  • Immunohistochemistry (IHC)5,6
    • Uses specific monoclonal antibodies to detect overexpression of the ALK fusion protein
  • Next-generation sequencing (NGS)7
    • NGS allows massive parallel sequencing for the identification of potentially targetable genetic alterations in tumors, such as ALK8
  • Currently, FISH, IHC, and NGS are the only testing methods FDA-approved for clinical application in detecting ALK+ NSCLC4,5,7

Other testing methods are under investigation, including reverse transcriptase-polymerase chain reaction (RT-PCR).9,10

  • RT-PCR is a technique that utilizes RNA extraction to detect ALK gene fusions, such as EML4-ALK 9, 10


ALK=anaplastic lymphoma kinase; CAP=College of American Pathologists; DNA=deoxyribonucleic acid; EML4=echinoderm microtubule-associated protein-like 4; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer; RNA=ribonucleic acid.


  1. Solomon B, Wilner KD, Shaw AT. Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Clin Pharmacol Ther. 2014;95:15-23. PMID: 24091716
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2018. © National Comprehensive Cancer Network, Inc 2018. All rights reserved. Published April 26, 2018. Accessed June 4, 2018. To view the most recent and complete version of the guideline, go online to NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.
  3. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology. Arch Pathol Lab Med. 2013;137:828-860. PMID: 23551194
  4. Weickhardt AJ, Aisner DL, Franklin WA, Varella-Garcia M, Doebele RC, Camidge DR. Diagnostic assays for identification of anaplastic lymphoma kinase-positive non-small cell lung cancer. Cancer. 2013;119:1467-1477. PMID: 23280244
  5. Marchetti A, Di Lorito A, Pace MV, et al. ALK protein analysis by IHC staining after recent regulatory changes: a comparison of two widely used approaches, revision of the lierature, and a new testing algorithm. J Thorac Oncol. 2016;11:487-495. PMID: 26916631
  6. Mino-Kenudson M, Chirieac LR, Law K, et al. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry. Clin Cancer Res. 2010;16:1561-1571. PMID: 20179225
  7. U.S. Food and Drug Administration. Foundation One CDX. Accessed June 4, 2018.
  8. Vigneswaran J, Tan Y-HC, Murgu SD, et al. Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation. Oncotarget. 2016;7:18876-18886. PMID: 26934441
  9. Wang Y, Liu Y, Zhao C, et al. Feasibility of cytological specimens for ALK fusion detection in patients with advanced NSCLC using the method of RT-PCR. Lung Cancer. 2016;94:28-34. PMID: 26973203
  10. Soda M, Isobe K, Inoue A, et al. A prospective PCR-based screening for the EML4-ALK oncogene in non-small cell lung cancer. Clin Cancer Res. 2012;18:5682-5689. PMID: 22908099