Detecting ALK+ NSCLC

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

NCCN and CAP clinical guidelines recommend that patients with NSCLC be routinely tested for ALK+ disease.2,3

ALK may be detected by using a variety of methods4-7

  • 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 fusion and amplification
    • Currently, only FISH is FDA approved for clinical application in NSCLC
  • Other testing methods are under investigation, including immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR)5-7
    • IHC uses antibodies to detect overexpression of the ALK tyrosine kinase domain on tissue sections6,7

ALK=anaplastic lymphoma kinase; CAP=College of American Pathologists; DNA=deoxyribonucleic acid; NCCN=National Comprehensive Cancer Network; NSCLC=non-small cell lung cancer.


  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.4.2014. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Published March 11, 2015. Accessed November 16, 2015. 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. Wong DW, Leung EL, So KK, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 2009;115:1723-1733. PMID: 19170230
  6. Yi ES, Boland JM, Maleszewski JJ, et al. Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH. J Thorac Oncol. 2011;6:459-465. PMID: 21278610
  7. 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