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Advantages

IHC is widely available, inexpensive, and efficient in terms of the amount of tissue required, and has a fast turnaround time (typically within 24 hours).

Several recent studies suggest that pan-TRK IHC is a sensitive technique for detecting NTRK gene fusions [1-5]. Sensitivity was 93%–97% for infantile fibrosarcoma [2], paediatric mesenchymal tumours [3], and solid tumours [1]. Another study reported a lower overall sensitivity of 75% across common solid tumours [4]. However, concordance between IHC and RNA-based NGS (Archer fusion assay) was 88%–89% for NTRK1 and NTRK2 gene fusions, compared with 55% for NTRK3 gene fusions [4].

The advantages of IHC are summarised in the following table.

Advantages of IHC for Testing of NTRK Gene Fusions

Advantages

  • Useful for screening as it is sensitive
    • Detects most NTRK1-3 gene fusions via protein overexpression
  • Low cost
  • Can be used even in low prevalence tumours
  • Fast turnaround time

References

  1. 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.
  2. 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.
  3. 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.
  4. Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol 2019; 32.
  5. Brčić I, Godschachner TM, Bergovec M et al. Broadening the spectrum of NTRK rearranged mesenchymal tumors and usefulness of pan-TRK immunohistochemistry for identification of NTRK fusions. Mod Pathol. 2021; 34(2):396-407.

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