NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated liposarcomas.

The () 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 genes, is a useful tool to detect tumors with or without gene alterations, due to high negative predictive value. Though it is well known that pan-TRK immunopositivity is usually not connected to fusion, the role of other possible genetic alterations is under-researched. In our previous work, we found 3 amplified cases out of 6 cases with recurrent 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 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 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 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 amplifications which might be important in the TRK inhibition therapy.