Open AccessThe 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
Author(s) -
Mieke Van Bockstal,
Gabriela Beniuga,
Ligia Craciun,
David Creytens,
Franceska Dedeurwaerdere,
Philippe Delvenne,
Pieter Demetter,
Bart De Wiest,
Koen De Winne,
Lionel Habran,
Patrick Pauwels,
Ivan Théate,
Sara Vander Borght,
K. Van Steen,
Birgit Weynand
Publication year - 2022
Publication title -
pathobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.941
H-Index - 53
eISSN - 1423-0291
pISSN - 1015-2008
DOI - 10.1159/000522426
Subject(s) - trk receptor , immunohistochemistry , tropomyosin receptor kinase a , tropomyosin receptor kinase b , tropomyosin receptor kinase c , tropomyosin , neurotrophin , medicine , receptor , biology , neurotrophic factors , microbiology and biotechnology , platelet derived growth factor receptor , myosin , growth factor
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.