The Pan-TRK Antibody is a Sensitive and Specific Tool for the Detection of NTRK Fusion Genes

Abstract

Pan-TRK antibodies have been used to detect gene fusions in diverse types of tumors. Several tyrosine receptor kinases (TRK) inhibitors have recently been developed and have shown good response rates in neoplasms with NTRK; therefore, identifying these fusions is an essential tool in assessing treatment options for certain oncological diseases. Various algorithms have been designed to diagnose and detect NTRK fusions to optimize time and resources. This study explores the use of immunohistochemistry (IHC) as a screening method for NTRK fusions by comparing next-generation sequencing (NGS) and IHC to evaluate the pan-TRK antibody's performance as a marker for NTRK rearrangements. The present work studied 164 formalin-fixed paraffin-embedded blocks of different solid tumors. Two pathologists confirmed the diagnosis and selected the correct area to assess with IHC and NGS. Specific cDNAs were generated for the genes involved. NTRK fusions were identified in 4 patients positive for the pan-TRK antibody through NGS. The identified fusions were NTRK1-TMP3, NTRK3-EML4, and NTRK3-ETV6. That shows sensitivity and specificity of 100% and 98%, respectively. NTRK fusions were identified in 4 patients positive for the pan-TRK antibody through NGS. IHC tests (with the pan-TRK antibody) are a sensitive and specific method for identifying the presence of NTRK1-3 fusions.