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CC BY 4.0 · Brazilian Journal of Oncology 2024; 20: e-20240456
DOI: 10.5935/2526-8732.20240456
Original Article
Pediatric Oncology

Immunohistochemistry and next-generation sequencing for NTRK fusion detection in differentiated thyroid cancer of children, adolescents and young adults

Ana Clara Oliveira Tosta Telles 
1   Federal University of Bahia, Department of Biorregulation, Health & Sciences Institute, Salvador - Bahia, Brazil
,
Gabriel Jeferson Rodríguez Machado 
1   Federal University of Bahia, Department of Biorregulation, Health & Sciences Institute, Salvador - Bahia, Brazil
,
Juliana Lima von-Ammon 
1   Federal University of Bahia, Department of Biorregulation, Health & Sciences Institute, Salvador - Bahia, Brazil
,
Rafael Reis Campos da-Matta 
1   Federal University of Bahia, Department of Biorregulation, Health & Sciences Institute, Salvador - Bahia, Brazil
,
Taíse Lima Cerqueira de-Oliveira 
1   Federal University of Bahia, Department of Biorregulation, Health & Sciences Institute, Salvador - Bahia, Brazil
,
Fabyan Esberard de Lima Beltrão 
2   Federal University of Paraíba, Lauro Wanderley University Hospital, João Pessoa - Paraíba, Brazil
,
Alexandre Rolim da-Paz 
2   Federal University of Paraíba, Lauro Wanderley University Hospital, João Pessoa - Paraíba, Brazil
,
Fabio Hecht 
3   Federal University of Rio de Janeiro, The Institute of Biophysics Carlos Chagas Filho, Rio de Janeiro - Rio de Janeiro, Brazil
,
Guilherme de Castro Lopes 
4   Pardini Group, Department of Molecular Genetics, Vespasiano - Minas Gerais, Brazil
,
Leonardo Freitas Boaventura Rios 
5   State University of Feira de Santana, Department of Health, Feira de Santana - Bahia, Brazil
,
Bruno da Silva Lisboa 
5   State University of Feira de Santana, Department of Health, Feira de Santana - Bahia, Brazil
,
Helton Estrela Ramos 
1   Federal University of Bahia, Department of Biorregulation, Health & Sciences Institute, Salvador - Bahia, Brazil
› Author Affiliations Financial support: none to declare.
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ABSTRACT

Introduction: Pan-TRK immunohistochemistry staining can assess the protein expression from NTRK gene fusions. A little is known about its utility in differentiated thyroid cancer samples from children, adolescents, and young adults patients. Objective:Investigate pan-TRKimmunohistochemistry sensitivity and specificity in differentiated thyroid cancer samples from children, adolescents, and young adults patients.

Methods: Tumor samples obtained from 79 children, adolescents, and young adults patients (age <21 years) diagnosed with differentiated thyroid cancer between January, 2010 and January, 2021 were retrospectively recruited from four health centers from state of Bahia e Paraíba, Brazil. NTRK gene fusion testing of all archival FFPE tumor samples: pan-TRK immunohistochemistry staining for TRKA, TRKB and TRKC protein expression were performed and then analyzed with RNA-based nextgeneration sequencing assay to confirm immunohistochemistry pan-TRK result and elucidate fusion partner.

Results: Pan-TRK immunohistochemistry: 3 of 79 cases had positive pan-TRK expression: next-generation sequencing; 4 were identified with NTRK gene fusion, pan-TRK immunohistochemistry was negative in all 4 NTRK next-generation sequencing-positive cases. 25 of 79 NTRK next-generation sequencing-negative control cases had concordant negative pan-TRK immunohistochemistry results. Therefore, our rate of false positive pan-TRK immunohistochemistry results was 3/25 (12%). The overall results for pan-TRK immunohistochemistry in our cohort of next-generation sequencing-negative cases was: (i) sensitivity (0%), (ii) specificity (96%), (iii) positive predictive value (94.7%), (iv) negative predictive value (91%).

Conclusion: Pan-TRK immunohistochemistry was not a tissue-efficient screen for NTRK fusions in differentiated thyroid cancer from children, adolescents, and young adults patients. This is the largest cohort of from children, adolescents, and young adults differentiated thyroid cancer cases stained with pan-TRK immunohistochemistry, and it is the first to detail the sensitivity and specificity of pan-TRK immunohistochemistry regarding the data obtained by targeted RNA-based next-generation sequencing panel in differentiated thyroid cancer.

RESUMO

Introdução: A coloração imuno-histoquímica Pan-TRK pode avaliar a expressão proteica de fusões de genes NTRK. Pouco se sabe sobre sua utilidade em amostras diferenciadas de câncer de tireoide de crianças, adolescentes e adultos jovens. Objetivo: Investigar a sensibilidade e especificidade da imuno-histoquímica pan-TRK em amostras diferenciadas de câncer de tireoide de pacientes crianças, adolescentes e adultos jovens.

Métodos: Amostras tumorais obtidas de 79 pacientes crianças, adolescentes e adultos jovens (idade <21 anos) com diagnóstico de câncer diferenciado de tireoide entre janeiro de 2010 e janeiro de 2021 foram recrutadas, retrospectivamente, em quatro centros de saúde dos estados da Bahia e Paraíba, Brasil. Teste de fusão genética NTRK de todas as amostras de tumor FFPE arquivadas: coloração imuno-histoquímica pan-TRK para expressão da proteína TRKA, TRKB e TRKC foi realizada e depois analisada com ensaio de sequenciamento de próxima geração baseado em RNA, para confirmar o resultado imuno- histoquímico pan-TRK e elucidar o parceiro de fusão.

Resultados: Imunohistoquímica pan-TRK: 3 de 79 casos tiveram expressão pan-TRK positiva: sequenciamento de próxima geração; 4 foram identificados com fusão do gene NTRK, a imuno-histoquímica pan-TRK foi negativa em todos os 4 casos positivos para sequenciamento de próxima geração de NTRK. 25 dos 79 casos de controle negativo para sequenciamento de próxima geração de NTRK tiveram resultados de imuno-histoquímica pan-TRK negativos concordantes. Portanto, nossa taxa de resultados de imuno-histoquímica pan-TRK falsos positivos foi de 3/25 (12%). Os resultados gerais da imuno- histoquímica pan-TRK em nossa coorte de casos negativos para sequenciamento de próxima geração foram: (i) sensibilidade (0%), (ii) especificidade (96%), (iii) valor preditivo positivo (94,7%), (iv) valor preditivo negativo (91%).

Conclusão: A imuno-histoquímica pan-TRK não foiuma triagem tecidualmente eficiente para fusões de NTRK em pacientes com câncer diferenciado de tireoide em crianças, adolescentes e adultos jovens. Esta é a maior coorte de casos de câncer diferenciado de tireoide de crianças, adolescentes e adultos jovens corados com imunohistoquímica pan-TRK, e é a primeira a detalhar a sensibilidade e especificidade da imunohistoquímica pan-TRK em relação aos dados obtidos por RNA direcionado baseado em um painel de sequenciamento de próxima geração no câncer diferenciado de tireoide.

Keywords:

Immunohistochemistry - Thyroid cancer, Papillary - Child - Adolescent

Descritores:

Imunohistoquímica - Câncer papilífero de tireoide - Criança - Adolescente


Publication History

Received: 17 November 2023

Accepted: 19 March 2024

Article published online:
02 May 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Ana Clara Oliveira Tosta Telles, Gabriel Jeferson Rodríguez Machado, Juliana Lima von-Ammon, Rafael Reis Campos da-Matta, Taíse Lima Cerqueira de-Oliveira, Fabyan Esberard de Lima Beltrão, Alexandre Rolim da-Paz, Fabio Hecht, Guilherme de Castro Lopes, Leonardo Freitas Boaventura Rios, Bruno da Silva Lisboa, Helton Estrela Ramos. Immunohistochemistry and next-generation sequencing for NTRK fusion detection in differentiated thyroid cancer of children, adolescents and young adults. Brazilian Journal of Oncology 2024; 20: e-20240456.
DOI: 10.5935/2526-8732.20240456
 

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