The neurotrophic tyrosine kinase receptor ( NTRK ) 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 NTRK1-2-3
genes, is a useful tool to detect tumors with or without NTRK gene alterations, due
to high negative predictive value. Though it is well known that pan-TRK immunopositivity
is usually not connected to NTRK fusion, the role of other possible genetic alterations
is under-researched. In our previous work, we found 3 NTRK1 amplified cases out of
6 cases with recurrent NTRK1 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 NTRK1-2-3 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 NTRK 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 NTRK 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 NTRK amplifications which might be important in
the TRK inhibition therapy.
