# Evaluation of NTRK Fusions Detection Method in Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma

## TL;DR

This study evaluates the effectiveness of using IHC and NGS to detect NTRK fusions in esophageal and gastric cancers, finding that NTRK fusions are rare in these cancers.

## Contribution

The study confirms the rarity of NTRK fusions in esophageal and gastric cancers and highlights the limitations of IHC screening for TRK protein.

## Key findings

- TRK protein was expressed in 10 out of 254 ESCC cases but none of the 401 GC cases.
- NGS and FISH analyses found no NTRK fusions in the TRK-positive ESCC cases.
- In silico analysis confirmed the low prevalence of NTRK fusions in these cancers.

## Abstract

Neurotrophic tyrosine receptor kinase (NTRK) fusions function as oncogenes and have been targeted by TRK inhibitors with excellent clinical outcomes. The international expert consensus recommends immunohistochemical (IHC) screening for TRK protein followed by next generation sequencing (NGS) to measure expression of NTRK fusions for tumors with low NTRK fusion expression. To confirm the clinical utility of this recommendation in esophageal and gastric cancers, total TRK protein expression was measured by IHC using anti-pan-TRK antibody in 254 esophageal squamous cell carcinoma (ESCC) and 401 gastric adenocarcinoma (GA) samples. Subsequently, DNA-based NGS and fluorescence in situ hybridization (FISH) were performed for tumors expressing TRK to measure NTRK fusion expression. Further, expression of NTRK fusions was evaluated in esophageal and gastric cancers using public databases. IHC staining revealed TRK was expressed in 10 out of 254 ESCC and 0 out of 401 GC cases. NGS and FISH analyses were performed for 10 TRK positive ESCC cases, identifying that none of these cases harbored NTRK fusions. In silico analyses further confirmed that NTRK fusions are rarely present in esophageal and gastric cancers. IHC screening for TRK protein is recommended to detect NTRK fusions, but this method may include many false-positives cases based on the sequencing analysis.