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Detection of <i>NTRK</i> Fusions and TRK Expression and Performance of pan-TRK Immunohistochemistry in Routine Diagnostics: Results from a Nationwide Community-Based Cohort
oleh: Bart Koopman, Chantal C. H. J. Kuijpers, Harry J. M. Groen, Wim Timens, Ed Schuuring, Stefan M. Willems, Léon C. van Kempen
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2022-03-01 |
Deskripsi
Gene fusions involving <i>NTRK1</i>, <i>NTRK2,</i> and <i>NTRK3</i> are rare drivers of cancer that can be targeted with histology-agnostic inhibitors. This study aimed to determine the nationwide landscape of <i>NTRK</i>/TRK testing in the Netherlands and the usage of pan-TRK immunohistochemistry (IHC) as a preselection tool to detect NTRK fusions. All pathology reports in 2017–2020 containing the search term ‘TRK’ were retrieved from the Dutch Pathology Registry (PALGA). Patient characteristics, tumor histology, <i>NTRK</i>/TRK testing methods, and reported results were extracted. <i>NTRK</i>/TRK testing was reported for 7457 tumors. Absolute testing rates increased from 815 (2017) to 3380 (2020). Tumors were tested with DNA/RNA-based molecular assay(s) (48%), IHC (47%), or in combination (5%). A total of 69 fusions involving <i>NTRK1</i> (<i>n</i> = 22), <i>NTRK2</i> (<i>n</i> = 6) and <i>NTRK3</i> (<i>n</i> = 41) were identified in tumors from adult (<i>n</i> = 51) and pediatric (<i>n</i> = 18) patients. In patients tested with both IHC and a molecular assay (<i>n</i> = 327, of which 29 <i>NTRK</i> fusion-positive), pan-TRK IHC had a sensitivity of 77% (95% confidence interval (CI), 56–91) and a specificity of 84% (95% CI, 78–88%). These results showed that pan-TRK IHC has a low sensitivity in current routine practice and warrants the introduction of quality guidelines regarding the implementation and interpretation of pan-TRK IHC.