Real-world challenges in undertaking NTRK fusion testing in non-small cell lung cancer

Ashleigh Poh; Abdelaziz Sammour; Jared Mathai; Joanne Peverall; Chris Van Vliet; Khashayar Asadi; Sagun Parakh

doi:10.21037/jtd-23-113

Real-world challenges in undertaking NTRK fusion testing in non-small cell lung cancer

J Thorac Dis. 2023 Jul 31;15(7):3811-3817. doi: 10.21037/jtd-23-113. Epub 2023 Jul 11.

Authors

Ashleigh Poh^{1

2}, Abdelaziz Sammour³, Jared Mathai³, Joanne Peverall⁴, Chris Van Vliet⁵, Khashayar Asadi⁶, Sagun Parakh^{1

2

3}

Affiliations

¹ Olivia Newton-John Cancer Wellness and Research Centre, Heidelberg, Victoria, Australia.
² La Trobe University School of Cancer Medicine, Bundoora, Victoria, Australia.
³ Department of Medical Oncology, Austin Hospital, Heidelberg, Victoria, Australia.
⁴ PathWest, Department of Diagnostic Genomics, QEII Medical Centre, Nedlands, Western Australia, Australia.
⁵ PathWest, Department of Anatomical Pathology, QEII Medical Centre, Nedlands, Western Australia, Australia.
⁶ Department of Pathology, Austin Hospital, Heidelberg, Victoria, Australia.

Abstract

Background: We performed a retrospective analysis to determine the incidence of neurotrophic tropomyosin-receptor kinase (NTRK) fusion in non-small cell lung cancer (NSCLC).

Methods: Archival NSCLC tissues between 2018-2020 were screened by immunohistochemistry (IHC) with IHC-positive cases undergoing confirmatory molecular analysis. Correlative clinicopathologic parameters were collected.

Results: Of 289 samples analyzed, 10 (3.5%) cases had NTRK expression on IHC. The median age of patients with NTRK-positivity on IHC was 74.9 (range, 44-88) years and 70% had a smoking history. The cohort included seven adenocarcinomas and one each squamous cell carcinoma, large-cell neuroendocrine and not otherwise specified histologies. PDL1 expression was ≤50% in five cases. Concurrent EGFR mutations were detected in three cases, with two cases also showing a PIK3CA E542K mutation and MET amplification, respectively. Due to insufficient tumor material, RNA-sequencing was undertaken in only one IHC-positive case, with the other nine cases analyzed by Fluorescent in-situ Hybridisation. A NTRK fusion, EML4-NTRK3 gene fusion was detected in one patient, a frequency of 0.35%.

Conclusions: NTRK fusions in NSCLC are rare. This study highlights real world diagnostic challenges regarding NTRK testing, such as requirements of adequate tumor tissue and appropriate testing methodologies.

Keywords: Neurotrophic tropomyosin-receptor kinase (NTRK); fluorescence in situ hybridization (FISH); immunohistochemistry (IHC); incidence; non-small cell lung cancer (NSCLC).