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Fluorescent In Situ Hybridization Must be Preferred to pan-TRK Immunohistochemistry to Diagnose NTRK3-rearranged Gastrointestinal Stromal Tumors (GIST).
Castillon, Marine; Kammerer-Jacquet, Solène-Florence; Cariou, Mélanie; Costa, Sebastian; Conq, Gwenael; Samaison, Laura; Douet-Guilbert, Nathalie; Marcorelles, Pascale; Doucet, Laurent; Uguen, Arnaud.
Afiliação
  • Castillon M; Department of Pathology.
  • Kammerer-Jacquet SF; Departement of Pathology, CHU Rennes.
  • Cariou M; Registre des cancers digestifs du Finistère EA7479 SPURBO, Université de Bretagne Occidentale.
  • Costa S; Ouest Pathologie, Rennes.
  • Conq G; Ouest Pathologie.
  • Samaison L; Ouest Pathologie, Quimper, France.
  • Douet-Guilbert N; Cytogenetics Unit, Department of Genetics, CHRU Brest.
  • Marcorelles P; Department of Pathology.
  • Doucet L; Department of Pathology.
  • Uguen A; Department of Pathology.
Appl Immunohistochem Mol Morphol ; 29(8): 626-634, 2021 09 01.
Article em En | MEDLINE | ID: mdl-33758144
ABSTRACT
Tyrosine kinase inhibitors have revolutionized the treatment of patients with gastrointestinal stromal tumors (GISTs). Nevertheless, some GISTs do not contain any targetable KIT or PDGFRA mutations classically encountered in this field. Novel approved therapies targeting TRK chimeric proteins products of NTRK genes fusions consist in a promising approach to treat some patients with GISTs lacking any identified driver oncogenic mutation in KIT, PDGFRA or BRAF genes. Thus, an adequate testing strategy permitting to diagnose the rare NTRK-rearranged GISTs is required. In this work, we studied about the performances of pan-TRK immunohistochemistry (IHC) and NTRK1/2/3 fluorescent in situ hybridization in a series of 39 GISTs samples. Among 22 patients with GISTs lacking KIT or PDGFRA mutations, BRAFV600E IHC permitted to diagnose 2/22 (9%) BRAFV600E-mutated GISTs and, among the 20 KIT, PDGFRA, and BRAF wild type tumors, 1/20 (5%), NTRK3-rearranged tumor was diagnosed using NTRK3 fluorescent in situ hybridization. Pan-TRK IHC using EPR17341 and A7H6R clones was negative in this NTRK3-rearranged sample. Pan-TRK IHC was frequently positive in NTRK not rearranged tumors without (24 samples analyzed) or with (15 samples analyzed) KIT or PDGFRA mutations with major discrepancies between the 2 IHC clones (intraclass correlation coefficient of 0.3042). Given the new therapeutic opportunity offered by anti-TRK targeted therapies to treat patients with advanced cancers including GISTs, it is worth to extend molecular analysis to NTRK fusions testing in KIT, PDGFRA, and BRAF wild type GISTs. Pan-TRK IHC appears not relevant in this field but performing a simple NTRK3 fluorescent in situ hybridization test consists in a valuable approach to identify the rare NTRK3-rearranged GISTs treatable using anti-TRK therapies.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rearranjo Gênico / Hibridização in Situ Fluorescente / Receptor trkC / Tumores do Estroma Gastrointestinal / Proteínas de Neoplasias Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adult / Aged / Aged80 / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rearranjo Gênico / Hibridização in Situ Fluorescente / Receptor trkC / Tumores do Estroma Gastrointestinal / Proteínas de Neoplasias Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Adult / Aged / Aged80 / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article