NTRK protein expression in NSCLC and its clinicopathological correlation

Non-small cell lung cancer (NSCLC) is a complex disease with diverse clinical and molecular characteristics. Since the discovery of the oncogenic neurotrophic receptor tyrosine kinase (NTRK) gene fusion in colorectal cancer in 1986, its understanding has gradually progressed. NTRK's relevance is crucial to understanding some tumor development and how specific tyrosine receptor kinase inhibitors (TRKI) work. NTRK1, NTRK2, and NTRK3 (encoding the neurotrophin receptors TRKA, TRKB, and TRKC, respectively) rearrangement induces high tumor transforming ability. This study investigates the clinical relevance of NTRK immunohistochemistry in NSCLC patients in a cohort of 482 patients from Karolinska University Hospital with detailed clinical and pathological studies. Immunohistochemical staining for NTRK expression was performed, and the results were correlated with patient demographics, histological subtypes, tumor extent, and staging. Our findings revealed that NTRK expression, predominantly membranous and cytoplasmic, was detected in 22 out of 482 cases (4.56%). Notably, NTRK expression was more frequently observed in squamous-cell carcinoma (SqCC) than in adenocarcinoma (AdCa). Clinical correlations indicated a significant association between NTRK expression and histologic subtypes (p<0.001) and grade of differentiation (p=0.036). However, no significant correlations were observed with age, sex, tumor size, staging, or OS. NTRK immunohistochemistry represents a potential biomarker for a subset of NSCLC patients, particularly those with SqCC histology. Understanding the clinical implications of NTRK expression may contribute to personalized treatment strategies in NSCLC.