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The use of pan-tropomyosin receptor kinase immunohistochemistry as a screening tool for the detection of neurotrophic tropomyosin-related kinase fusions : real-world data from a national multicentric retrospective study

Mieke R. Van Bockstal, Gabriela Beniuga, Ligia Craciun, David Creytens (UGent) , Franceska Dedeurwaerdere, Philippe Delvenne, Pieter Demetter, Bart De Wiest, Koen Dewinne, Lionel Habran, et al.
(2022) PATHOBIOLOGY. 89(6). p.393-406
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Abstract
Introduction: The neurotrophic tropomyosin-related kinase (NTRK) genes encode the tropomyosin receptor kinases (TRKs). Patients with solid tumors harboring an oncogenic NTRK fusion are eligible for treatment with TRK inhibitors. NTRK fusion is often associated with TRK overexpression. Pan-TRK immunohistochemistry (IHC) is used to screen for NTRK fusions, but immunoreactivity patterns are poorly defined. Methods: Data on pan-TRK immunoreactivity patterns in 2,669 solid tumors (comprising carcinomas, sarcomas, and melanocytic lesions) were retrospectively collected by nine laboratories and comprised tumor type, percentage of pan-TRK-positive tumor cells, staining intensity, cytoplasmic, membrane and/or nuclear staining pattern, and the presence or absence of NTRK fusion. Results: Overall, 2,457 tumors (92%) were pan-TRK negative and 212 neoplasms (8%) were pan-TRK positive. Twenty-two pan-TRK-positive tumors (0.8%) harbored an NTRK fusion, representing 10% of all pan-TRK-positive tumors. Cytoplasmic immunoreactivity was most often observed, followed by membrane immunoreactivity. Nuclear pan-TRK positivity was least frequent, but was most often (33%) associated with NTRK fusion. Conclusion: Pan-TRK IHC can be used to screen for NTRK fusions, especially in commonly diagnosed solid tumors with low NTRK fusion prevalence. In case of pan-TRK immunoreactivity, regardless of its intensity and tumor cell percentage, subsequent molecular tests should be performed to formally confirm the presence or absence of NTRK fusions.
Keywords
Cell Biology, Molecular Biology, General Medicine, Pathology and Forensic Medicine, Immunohistochemistry, Gene fusion, Next-generation sequencing, Pan-tropomyosin receptor kinase, Neurotrophic tropomyosin-related kinase, POSITIVE SOLID TUMORS, TRK IMMUNOHISTOCHEMISTRY, NTRK FUSIONS, SALIVARY-GLAND, GENE FUSION, REARRANGEMENTS, LAROTRECTINIB, ENTRECTINIB, FREQUENCY, CANCERS

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MLA
Van Bockstal, Mieke R., et al. “The Use of Pan-Tropomyosin Receptor Kinase Immunohistochemistry as a Screening Tool for the Detection of Neurotrophic Tropomyosin-Related Kinase Fusions : Real-World Data from a National Multicentric Retrospective Study.” PATHOBIOLOGY, vol. 89, no. 6, 2022, pp. 393–406, doi:10.1159/000522426.
APA
Van Bockstal, M. R., Beniuga, G., Craciun, L., Creytens, D., Dedeurwaerdere, F., Delvenne, P., … Weynand, B. (2022). The use of pan-tropomyosin receptor kinase immunohistochemistry as a screening tool for the detection of neurotrophic tropomyosin-related kinase fusions : real-world data from a national multicentric retrospective study. PATHOBIOLOGY, 89(6), 393–406. https://doi.org/10.1159/000522426
Chicago author-date
Van Bockstal, Mieke R., Gabriela Beniuga, Ligia Craciun, David Creytens, Franceska Dedeurwaerdere, Philippe Delvenne, Pieter Demetter, et al. 2022. “The Use of Pan-Tropomyosin Receptor Kinase Immunohistochemistry as a Screening Tool for the Detection of Neurotrophic Tropomyosin-Related Kinase Fusions : Real-World Data from a National Multicentric Retrospective Study.” PATHOBIOLOGY 89 (6): 393–406. https://doi.org/10.1159/000522426.
Chicago author-date (all authors)
Van Bockstal, Mieke R., Gabriela Beniuga, Ligia Craciun, David Creytens, Franceska Dedeurwaerdere, Philippe Delvenne, Pieter Demetter, Bart De Wiest, Koen Dewinne, Lionel Habran, Patrick Pauwels, Ivan Theate, Sara Vander Borght, Kris Van Der Steen, and Birgit Weynand. 2022. “The Use of Pan-Tropomyosin Receptor Kinase Immunohistochemistry as a Screening Tool for the Detection of Neurotrophic Tropomyosin-Related Kinase Fusions : Real-World Data from a National Multicentric Retrospective Study.” PATHOBIOLOGY 89 (6): 393–406. doi:10.1159/000522426.
Vancouver
1.
Van Bockstal MR, Beniuga G, Craciun L, Creytens D, Dedeurwaerdere F, Delvenne P, et al. The use of pan-tropomyosin receptor kinase immunohistochemistry as a screening tool for the detection of neurotrophic tropomyosin-related kinase fusions : real-world data from a national multicentric retrospective study. PATHOBIOLOGY. 2022;89(6):393–406.
IEEE
[1]
M. R. Van Bockstal et al., “The use of pan-tropomyosin receptor kinase immunohistochemistry as a screening tool for the detection of neurotrophic tropomyosin-related kinase fusions : real-world data from a national multicentric retrospective study,” PATHOBIOLOGY, vol. 89, no. 6, pp. 393–406, 2022.
@article{8748180,
  abstract     = {{Introduction: The neurotrophic tropomyosin-related kinase (NTRK) genes encode the tropomyosin receptor kinases (TRKs). Patients with solid tumors harboring an oncogenic NTRK fusion are eligible for treatment with TRK inhibitors. NTRK fusion is often associated with TRK overexpression. Pan-TRK immunohistochemistry (IHC) is used to screen for NTRK fusions, but immunoreactivity patterns are poorly defined. Methods: Data on pan-TRK immunoreactivity patterns in 2,669 solid tumors (comprising carcinomas, sarcomas, and melanocytic lesions) were retrospectively collected by nine laboratories and comprised tumor type, percentage of pan-TRK-positive tumor cells, staining intensity, cytoplasmic, membrane and/or nuclear staining pattern, and the presence or absence of NTRK fusion. Results: Overall, 2,457 tumors (92%) were pan-TRK negative and 212 neoplasms (8%) were pan-TRK positive. Twenty-two pan-TRK-positive tumors (0.8%) harbored an NTRK fusion, representing 10% of all pan-TRK-positive tumors. Cytoplasmic immunoreactivity was most often observed, followed by membrane immunoreactivity. Nuclear pan-TRK positivity was least frequent, but was most often (33%) associated with NTRK fusion. Conclusion: Pan-TRK IHC can be used to screen for NTRK fusions, especially in commonly diagnosed solid tumors with low NTRK fusion prevalence. In case of pan-TRK immunoreactivity, regardless of its intensity and tumor cell percentage, subsequent molecular tests should be performed to formally confirm the presence or absence of NTRK fusions.}},
  author       = {{Van Bockstal, Mieke R. and Beniuga, Gabriela and Craciun, Ligia and Creytens, David and Dedeurwaerdere, Franceska and Delvenne, Philippe and Demetter, Pieter and De Wiest, Bart and Dewinne, Koen and Habran, Lionel and Pauwels, Patrick and Theate, Ivan and Vander Borght, Sara and Van Der Steen, Kris and Weynand, Birgit}},
  issn         = {{1015-2008}},
  journal      = {{PATHOBIOLOGY}},
  keywords     = {{Cell Biology,Molecular Biology,General Medicine,Pathology and Forensic Medicine,Immunohistochemistry,Gene fusion,Next-generation sequencing,Pan-tropomyosin receptor kinase,Neurotrophic tropomyosin-related kinase,POSITIVE SOLID TUMORS,TRK IMMUNOHISTOCHEMISTRY,NTRK FUSIONS,SALIVARY-GLAND,GENE FUSION,REARRANGEMENTS,LAROTRECTINIB,ENTRECTINIB,FREQUENCY,CANCERS}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{393--406}},
  title        = {{The use of pan-tropomyosin receptor kinase immunohistochemistry as a screening tool for the detection of neurotrophic tropomyosin-related kinase fusions : real-world data from a national multicentric retrospective study}},
  url          = {{http://doi.org/10.1159/000522426}},
  volume       = {{89}},
  year         = {{2022}},
}
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