NTRK fusion analysis reveals enrichment in Middle Eastern BRAF wild-type PTC

Objective: Fusions involving neurotrophic tyrosine receptor kinase (NTRK) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as a predictor of targeted therapy since selective NTRK inhibitors are now approved in the US and Europe for patients with solid tumors harboring gene fusions. However, estimation of NTRK gene fusion/alteration frequency and its clinicopathological characteristics in papillary thyroid cancer (PTC) is limited, especially in a population with high incidence for PTC like Middle Eastern population. This study aims to characterize the NTRKgene fusion frequency and investigate the utility of pan-Trk immunohistochemistry (IHC) as predictor of NTRK fusion in a large cohort of Middle Eastern PTC. Methods: FISH analysis for NTRKgene fusions and pan-Trk IHC was performed on 315 Middle Eastern PTCs. Correlation of NTRKgene fusion and protein expression with clinicopathological markers and patient outcome were determined. Results: In our cohort, 6.0% (19/315) patients showed NTRKgene fusions and were significantly associated with pediatric PTC (P = 0.0143), lymph node metastasis (P = 0.0428) and BRAF WT tumors (P < 0.0001). Pan-Trk IHC was positive in 9.2% (29/315) of cases and significantly associated with NTRKfusions, with a sensitivity of 73.7% and specificity of 94.9% in this cohort. Conclusions: This study confirms the presence of NTRKfusions in Middle Eastern PTC which is significantly enriched in BRAF WT as well as pediatric age group and proposes the usefulness of IHC to screen for PTC patients with NTRKfusion that might benefit from TRK inhibitors.

Automated summary

This study reveals the presence of NTRK fusions in Middle Eastern PTC, particularly enriched in BRAF WT and pediatric age group, and suggests the utility of immunohistochemistry for screening PTC patients with NTRK fusion who may benefit from TRK inhibitors.