Previous Page Next Page

Applications in NTRK Gene Fusion Testing

NTRK gene fusions are rare but occur in diverse tumour types and cell lineages, posing a considerable challenge for detection, while also creating an opportunity for IHC to be used alongside molecular testing [1].

IHC can detect TRK protein overexpression as a surrogate for the possible presence of a NTRK gene fusion and may be considered as a screening tool when access to NGS is limited; where possible, molecular testing should be performed in those who test positive by IHC [2-6].

Application of IHC within NTRK gene fusion testing workflows has been reported in the literature. Rudzinski et al. proposed that moderate-to-strong diffuse cytoplasmic pan-TRK IHC staining can be considered diagnostic of NTRK1/NTRK2 gene fusions, while nuclear pan-TRK staining can be considered a diagnostic surrogate of ETV6-NTRK3 gene fusions [7]. In addition, Murphy et al. outlined a two-step diagnostic test to identify NTRK1, NTRK2, NTRK3, ROS1, and ALK rearrangements in tumour specimens, using IHC to screen negative specimens, followed by NGS to analyse putatively positive specimens [8]. IHC can also be used to validate the results of DNA-based targeted NGS screening by confirming that a novel DNA-level NTRK gene structural variant/rearrangement leads to overexpression of TRK, which would be consistent with a fusion [9, 10].

References

  1. Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J Hematol Oncol 2018; 11: 78.
  2. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731-747.
  3. Marchio C, Scaltriti M, Ladanyi M et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol. 2019 Jul 3. pii: mdz204. doi: 10.1093/annonc/mdz204. [Epub ahead of print].
  4. Albert CM, Davis JL, Federman N et al. TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening. J Clin Oncol 2019; 37: 513-524.
  5. Penault-Llorca F, Rudzinski ER, Sepulveda AR. Testing algorithm for identification of patients with TRK fusion cancer. J Clin Pathol 2019.
  6. Kummar S, Lassen UN. TRK Inhibition: A New Tumor-Agnostic Treatment Strategy. Target Oncol 2018; 13: 545-556.
  7. Rudzinski ER, Lockwood CM, Stohr BA et al. Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. Am J Surg Pathol 2018; 42: 927-935.
  8. Murphy DA, Ely HA, Shoemaker R et al. Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing. Appl Immunohistochem Mol Morphol 2017; 25: 513-523.
  9. Hechtman JF, Benayed R, Hyman DM et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol 2017; 41: 1547-1551.
  10. Hung YP, Fletcher CDM, Hornick JL. Evaluation of pan-TRK immunohistochemistry in infantile fibrosarcoma, lipofibromatosis-like neural tumour and histological mimics. Histopathology 2018; 73: 634-644.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings