Pan-TRK (clone EPR17341) is directed against the C-terminal region of TRK (tropomyosin receptor kinase) A, B, and C proteins, which are encoded by NTRK1, NTRK2, and NTRK3 genes respectively. Pan-TRK IHC staining is a useful screen for identification of NTRK protein overexpression caused by gene fusions. Correlation of IHC staining with molecular detection of TRK fusions is moderate; discrepant cases have been described. IHC screening is not recommended in neuroendocrine tumors, GISTs, gliomas, or adult sarcomas, as these tissues show positive staining in the absence of an NTRK translocation. Published sensitivity rates of IHC staining for detection of NTRK fusions (detected by molecular testing) are 95% and above. Follow-up molecular testing is available to confirm positivity and identify the specific NTRK gene rearranged and its fusion partner gene.
NTRK gene fusions have been reported in >20 tumor types. They occur in >90% of certain rare tumors and are considered essentially pathogenic in secretory breast cancer, congenital fibrosarcoma, congenital mesoblastic nephroma, and mammary analogue secretory carcinoma (MASC). Tumors with intermediate NTRK fusion frequencies (5-25%) include papillary thyroid cancer (PTC), GIST without KIT/PDGFRA/RAS mutations, spitzoid neoplasms, and certain pediatric gliomas. NTRK fusions are detected in <5% of a wide range of common tumors including non-small cell lung cancer (NSCLC, ~1%); pancreatic adenocarcinoma; head and neck squamous cell; breast, colorectal, and renal cell carcinoma; melanoma; and adult brain tumors such as astrocytoma and glioblastoma. Testing for NTRK fusions identifies patients who may be candidates for NTRK inhibitor therapy.
A formalin-fixed, paraffin-embedded (FFPE) tissue block is preferred specimen type
One (1) unbaked, unstained slide for H&E staining (required) and two to three (2-3) positively charged unstained slides (all cut at 4-5 microns) for each test/antibody ordered
Block and slide identifiers should be clearly written and match exactly with the specimen ID and specimen labeling as noted on the requisition.
Use cold pack for transport. Make sure cold pack is not in direct contact with specimen.
1. Albert CM, Davis JL, Federman H, et al. TRK fusion cancers in children: A clinical review and recommendations for screening. J Clin Oncol.2018;doi: 10.1200/JCO.18.00573.
2. Rudzinski ER, Lockwood CM, Stohr BA, et al. Pan-Trk IHC identifies NTRK rearrangements in pediatric mesenchymal tumors. Am J Surg Pathol. 2018; 42(7):927-935
3. Hechtman JF, Benayed R, Hyman DM, et al. Pan-Trk IHC is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol.2017;41(11):1547-1551.
4. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy.Nat Rev Clin Oncol.2018;15:731-747.
5. Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J Hematol Oncol.2018;11:78.