Investıgatıon of NTRK Fusıon in Non-Small Cell Lung Cancers by Immunohıstochemıcal and Molecular Methods

Abstract

Neurotrophic tyrosine receptor kinase (NTRK) fusions, which have been identified as a major genetic alteration in some tumors, have rarely been reported in more common tumors such as non-small cell lung carcinoma(NSCLC). In addition to immunohistochemical methods for NTRK fusion detection, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction and next generation sequencing tests are used molecularly. The aim of this study was to investigate to what extent NTRK gene fusion play a role in the tumorigenesis of NSCLC, associated with clinicopathologic parameters and prognosis. This retrospective study included 340 cases of NSCLC diagnosed in our institution. All cases were analyzed in terms of Pan-TRK immunohistochemical expression, clinicopathologic parameters and prognosis. Immunohistochemical Pan-TRK positivity was confirmed by reverse transcriptase-polymerase chain reaction. In cases in which NTRK fusion was detected by reverse transcriptase polymerase chain reaction, NTRK fusion was reconfirmed by fluorescence in situ hybridization. Immunohistochemical Pan-TRK (clone EPR17341) expression was observed in 25 (7.4%) cases. NTRK3 fusion was detected in 3 of these cases by reverse transcriptase-polymerase chain reaction test and confirmed by fluorescence in situ hybridization. Two NTRK fusion positive cases were squamous cell carcinoma and one case was adenocarcinoma. Our findings suggest that immunohistochemistry can be used as a screening test, but requires molecular confirmation. Our finding of NTRK3 fusion in squamous cell carcinomas with limited treatment options, suggests that the driver function of this gene may be more effective in this group.

Neurotrophic tyrosine receptor kinase (NTRK) fusions, which have been identified as a major genetic alteration in some tumors, have rarely been reported in more common tumors such as non-small cell lung carcinoma(NSCLC). In addition to immunohistochemical methods for NTRK fusion detection, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction and next generation sequencing tests are used molecularly. The aim of this study was to investigate to what extent NTRK gene fusion play a role in the tumorigenesis of NSCLC, associated with clinicopathologic parameters and prognosis. This retrospective study included 340 cases of NSCLC diagnosed in our institution. All cases were analyzed in terms of Pan-TRK immunohistochemical expression, clinicopathologic parameters and prognosis. Immunohistochemical Pan-TRK positivity was confirmed by reverse transcriptase-polymerase chain reaction. In cases in which NTRK fusion was detected by reverse transcriptase polymerase chain reaction, NTRK fusion was reconfirmed by fluorescence in situ hybridization. Immunohistochemical Pan-TRK (clone EPR17341) expression was observed in 25 (7.4%) cases. NTRK3 fusion was detected in 3 of these cases by reverse transcriptase-polymerase chain reaction test and confirmed by fluorescence in situ hybridization. Two NTRK fusion positive cases were squamous cell carcinoma and one case was adenocarcinoma. Our findings suggest that immunohistochemistry can be used as a screening test, but requires molecular confirmation. Our finding of NTRK3 fusion in squamous cell carcinomas with limited treatment options, suggests that the driver function of this gene may be more effective in this group. © 2025 Elsevier B.V., All rights reserved.