Abstract 2425: Prevalence of NTRK fusions and clinico-pathological characteristics of Middle Eastern papillary thyroid cancer revealed enrichment in BRAF wild-type PTC

Abstract

Abstract Fusions involving neurotrophic tyrosine receptor kinase (NTRK) are known oncogenic drivers in a broad range of tumor types. It recently gained attention as predictor of targeted therapy, since selective NTRK inhibitor are now approved in US and Europe for patients with solid tumor harboring gene fusions. However, estimation of NTRK gene fusion/alteration frequency and its clinico-pathological 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 NTRK gene fusion frequency using FISH analysis and investigate the utility of pan-Trk immunohistochemistry as predictor of NTRK fusion in a large cohort of Middle Eastern PTC. FISH analysis for NTRK gene fusions as well as immunohistochemical (IHC) staining was conducted on a cohort of 315 Middle Eastern PTC. Correlation of NTRK with clinico-pathological markers and patient outcome were determined. 6.0% (19/315) patients were identified with NTRK gene fusions and significantly associated with pediatric PTC, lymph node metastasis and BRAF wild-type. Pan-Trk IHC was positive in 9.2% (29/315) and significantly associated with NTRK gene fusion with a sensitivity of 73.7% and specificity of 94.9% in this cohort. In conclusion, this study confirms the presence of NTRK fusions in Middle Eastern PTC and mostly enriched in BRAF wild-type and pediatric age group and propose the usefulness of IHC to screen for PTC patients with NTRK fusion that might benefit from TRK inhibitors. Citation Format: Abdul K. Siraj, Rong Bu, Sandeep K. Parvathareddy, Yan Kong, Padmanaban Annaiyappanaidu, Saeeda O. Ahmed, Maha Al-Rasheed, Khawla S. Al-Kuraya. Prevalence of NTRK fusions and clinico-pathological characteristics of Middle Eastern papillary thyroid cancer revealed enrichment in BRAF wild-type PTC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2425.