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Can Pan-TRK Immunohistochemistry Identify NTRK Fusions in Lung Cancer?

By: Noelle Cutter, PhD
Posted: Sunday, August 1, 2021

A retrospective analysis published in Scientific Reports examined the use of immunohistochemistry with the pan-TRK antibody to detect NTRK fusions in non–small cell lung carcinoma. Luka Brcic, PhD, and colleagues from the Diagnostic and Research Institute of Pathology, Medical University of Graz, Austria, reported that pan-TRK expression in lung cancers is very low across histologic types, and confirmation of immunohistochemistry results should be validated using molecular methods.

“Our study has confirmed that protein expression does not imply the presence of NTRK1–3 gene fusions and has, therefore, to be verified, ideally by RNA-based massive parallel sequencing,” noted the authors.

From 1993 to 2012, a total of 387 lung carcinoma cases were examined and reevaluated according to WHO 2015 criteria and restaged using the 2017 UICC/AJCC. Immunohistochemical analysis was performed, and positive pan-TRK reactions were further analyzed using RNA massive parallel sequencing.

Of the 387 patients with lung cancer, 12 (3.1%) stained positive for TRK expression on immunohistochemical analysis. A total of 10 were squamous cell carcinomas, and 2 were large cell neuroendocrine carcinomas. Molecular analysis revealed that seven cases had no NTRK1–3 fusions and five cases had insufficient RNA quality to be analyzed. 

“However, whether the protein expression is also important for the therapeutic effect, even without fusion, and the real number of cases harboring these rare fusions that we miss using immunohistochemistry as a screening should be clarified in further studies,” cautioned the authors.

Disclosure: The study authors reported no conflicts of interest.

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