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. and (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 (<0.001) and grade of differentiation (=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.
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http://dx.doi.org/10.14670/HH-18-894 | DOI Listing |
Histol Histopathol
February 2025
Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
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.
View Article and Find Full Text PDFBioinform Adv
February 2025
Department of Molecular Medicine, Medical Biotechnology Institute, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316, Iran.
Motivation: Breast cancer (BC), with its rising prevalence and mortality rate, is one of the most significant human health issues. The family of transmembrane tyrosine kinases that promote neuronal growth includes the neurotrophic tyrosine kinase receptors (NTRKs). NTRK1-3 genes encode the members of this family.
View Article and Find Full Text PDFFront Pharmacol
February 2025
Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, China.
Background: The tyrosine receptor kinase inhibitor (TRKi) entrectinib is used to treat neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors and ROS1-positive patients. Despite its impressive efficacy against cancer, the clinical application is still limited by the central nervous system (CNS)-related toxicities. However, the precise mechanism of such CNS-related toxicities remains elusive.
View Article and Find Full Text PDFBMC Womens Health
February 2025
Department of Gynecologic Oncology, Yunnan Cancer Hospital/The Third Affiliated Hospital of Kunming Medical University/Peking University Cancer Hospital Yunnan, KunMing, 650118, People's Republic of China.
Background: Neurotrophic tyrosine receptor kinase (NTRK) rearranged spindle cell neoplasm is an emerging group of molecularly defined rare soft tissue tumors, often presenting with a monotonous spindle cell morphology, infiltrative growth, and co-expression of S-100 and CD34 proteins by immunohistochemistry (IHC). Accurate diagnosis necessitates the combination of morphology, immunohistochemistry, and molecular test results, with next-generation sequencing (NGS) as the gold standard. We present a rare case of NTRK rearranged spindle cell neoplasm of the uterine cervix and review the literature to highlight the current understanding of the diagnosis and treatment of this rare disease.
View Article and Find Full Text PDFClin Cancer Res
February 2025
University of California, San Diego, San Diego, CA, United States.
Introduction: Previous reports have described ETV6-NTRK3 fusion-positive gastrointestinal stromal tumors (GISTs) in cases lacking KIT, PDGFRA, RAS-pathway, or SDHx alterations. However, some investigators have questioned the rigor of these reports and the true existence of NTRK rearrangements in GIST. This study aims to: 1) resolve whether NTRK gene rearrangements exist in GIST; 2) review the relevant literature; and 3) demonstrate a case of NTRK fusion GIST.
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