{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:24:44Z","timestamp":1793118284542,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["por-journal.com"],"crossmark-restriction":true},"short-container-title":["Pathol. Oncol. Res."],"abstract":"<jats:p>The <jats:italic>neurotrophic tyrosine kinase receptor<\/jats:italic> (<jats:italic>NTRK<\/jats:italic>) gene family is of rising importance as their fusions are oncogenic, and specific target drugs are available to inhibit the chimera proteins. Pan-TRK antibody, which shows the overexpression of the <jats:italic>NTRK1-2-3<\/jats:italic> genes, is a useful tool to detect tumors with or without <jats:italic>NTRK<\/jats:italic> gene alterations, due to high negative predictive value. Though it is well known that pan-TRK immunopositivity is usually not connected to <jats:italic>NTRK<\/jats:italic> fusion, the role of other possible genetic alterations is under-researched. In our previous work, we found 3 <jats:italic>NTRK1<\/jats:italic> amplified cases out of 6 cases with recurrent <jats:italic>NTRK1<\/jats:italic> tyrosine kinase domain mutation pair, so we extended our investigation to a larger series to estimate amplification frequency. Pan-TRK immunopositivity was seen in 76 of the 132 dedifferentiated liposarcomas cases, followed by <jats:italic>NTRK1-2-3<\/jats:italic> break-apart FISH tests in 76 pan-TRK positive cases to detect oncogenic fusions or other copy number alterations of these genes. None of the pan-TRK immunopositive dedifferentiated liposarcomas showed absolutely certain sign of fusion, however, 18 (28%) cases showed amplification of one of the genes, 13 had polysomy, 34 were normal, 11 were not evaluable. The extent of pan-TRK immunoreaction showed a positive correlation (p = 0.002) with the <jats:italic>NTRK<\/jats:italic> status found by FISH. Analyzing publicly available data from large series of 265 liposarcoma samples consisting of both well-differentiated and dedifferentiated liposarcoma case, 23 (8.6%) cases showed a mutual exclusive amplification of the <jats:italic>NTRK<\/jats:italic> genomic loci in a non-preselected, independent patient population indicating that our findings are presented in other cohorts. Our results underline the so far not revealed frequent occurrence of <jats:italic>NTRK<\/jats:italic> amplifications which might be important in the TRK inhibition therapy.<\/jats:p>","DOI":"10.3389\/pore.2024.1611993","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T04:11:24Z","timestamp":1736223084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated 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