Detecting ROS1+ NSCLC

NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines®) recommend testing for ROS1+ disease in all patients with nonsquamous metastatic NSCLC1

ROS1+ NSCLC can be detected with various testing methods2

Immunohistochemistry (IHC)1-4

  • Uses specific monoclonal antibodies to detect overexpression of the ROS1 fusion protein2
  • Requires dedicated tissue and limits multiplexing3,4
  • Low specificity; molecular confirmation is necessary1

Fluorescence in situ hybridization (FISH)1,2,4,5

  • Uses “break-apart” probes to show ROS1 gene rearrangement2
  • Requires dedicated tissue4,5
  • May under-detect the FIG-ROS1 variant1

Next-generation sequencing (NGS)1,2,4-6

  • Multigene parallel sequencing assays2,4
  • Capable of detecting ROS1 fusions1
  • Provides information about multiple biomarkers, including rare and common mutations, and can typically use less tissue4,5
  • Turnaround time for results may be longer than with RT-PCR, IHC, or FISH6

Real-time polymerase chain reaction (RT-PCR)1,7

  • Reverse transcription from extracted RNA7
  • Fast and sensitive detection of specific fusion variants7
  • May not detect fusions in novel partners1

NCCN=National Comprehensive Cancer Network; NSCLC=non–small cell lung cancer; ROS1=ROS proto-oncogene 1.


  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.6.2018. © National Comprehensive Cancer Network, Inc 2018. All rights reserved. Published August 17, 2018. Accessed August 22, 2018. To view the most recent and complete version of the guideline, go online to NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  2. Bubendorf L, Büttner R, Al-Dayel F, et al. Virchows Arch. 2016;469(5):489-503. PMID: 27535289
  3. Sholl LM, Sun H, Butaney M, et al. Am J Surg Pathol. 2013;37(9):1441-1449. PMID: 23887156
  4. Su D, Zhang D, Chen K, et al. J Exp Clin Cancer Res. 2017;36(1):121. PMID: 28882180
  5. Rogers TM, Arnau GM, Ryland GL, et al. Sci Rep. 2017;7:42259. PMID: 28181564
  6. Hechtman JF, Benayed R, Hyman DM, et al. Am J Surg Pathol. 2017;41(11):1547-1551. PMID: 28719467
  7. Shan L, Lian F, Guo L, et al. PLoS ONE. 2015;10(3):e0120422. PMID: 25742289