PhD Scientific Days 2025

Pathological and Oncological Sciences III.

NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated liposarcomas

Előadó neve

Dr. Lippai Zoltán, PhD

Neptun code

TB5D81

Előadó munkahelye

Semmelweis University Department of Orthopedic Surgery; Budapesti Bajcsy-Zsilinszky Kórház - Onkopatológiai Diagnosztikai Kft

Előadó telefonszáma

+36204219462

Előadó e-mail címe

zollippai@gmail.com

Az előadás címe

NTRK amplification occurs frequently in pan-TRK immunopositive dedifferentiated liposarcomas

Szerző(k) neve és munkahelye

Dr. Zoltán Lippai, PhD¹

1: Semmelweis Egyetem ÁOK Patológiai és Kísérleti Rákkutató Intézet

Bemutatás módja

Szóbeli

Szekció

Pathological and Oncological Sciences III.

Language of the presentation

Hungarian

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

Introduction: 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.

Aims: We aimed to investigate the relation between pan-TRK immunopositivity and possible genetic alterations by using NTRK1/2/3 locus specific break apart probe set in order to estimate the frequency of genomic rearrangement of NTRK1-2-3 genes in dedifferentiated liposarcomas.

Methods: 132 individual cases of dedifferentiated liposarcomas with myogenic heterologous differentiation were selected. Immunohistochemistry with pan-TRK antibody was performed on tumor samples from these cases. Pan-TRK immunopositive cases were analyzed by FISH using NTRK1-2-3 break apart probes. Publicly available data sets were analysed for the presence of structural variants involving NTRK1/2/3 gene loci, in which 265 liposarcomas samples were included.

Result: Pan-TRK immunopositivity was seen in 76 of the 132 dedifferentiated liposarcoma cases. None of the pan-TRK immunopositive dedifferentiated liposarcomas showed absolutely certain sign of fusion, however, 18 (27.7%) cases showed amplification of one of the genes, 13 had polysomy, 34 were normal, 11 were not evaluable by NTRK1-2-3 break apart FISH. Analyzing publicly available data from large series of 265 liposarcoma samples, 23 (8.6%) cases showed a mutual exclusive amplification of the NTRK genomic loci in a non-preselected, independent patient population.

Conclusion: Our results underline the so far not revealed frequent occurrence of NTRK amplifications in pan-TRK immunpositive tumors which might be important in the TRK inhibition therapy.

Funding: One member of the research group received grant via EKÖP.

University

Semmelweis University

Supervisor

Zoltán Sápi Ph.D., D.Sc.

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

jóváhagyta

Előadó

5002

Start

17:00

End

17:15