Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma

Sci Rep. 2021 May 7;11(1):9785. doi: 10.1038/s41598-021-89373-3.

Abstract

In the last two decades, various therapies have been introduced for lung carcinoma patients, including tyrosine-kinase inhibitors for different mutations. While some of them are specific to specific tumor types, others, like NTRK1-3 fusions, are found in various solid tumors. The occurrence of an NTRK1,2 or 3 fusion acts as a biomarker for efficient treatment with NTRK inhibitors, irrespectively of the tumor type. However, the occurrence of the NTRK1-3 fusions in lung carcinomas is extremely rare. We performed a retrospective analysis to evaluate the applicability of immunohistochemistry with the pan-TRK antibody in the detection of NTRK fusions in lung carcinomas. The study cohort included 176 adenocarcinomas (AC), 161 squamous cell carcinomas (SCC), 31 large-cell neuroendocrine carcinomas (LCNEC), and 19 small cell lung carcinomas (SCLC). Immunohistochemistry (IHC) was performed using the pan-TRK antibody (clone EPR17341, Ventana) on tissue microarrays, while confirmation for all positive cases was done using RNA-based Archer FusionPlex MUG Lung Panel. On IHC staining, 12/387 samples (3.1%) demonstrated a positive reaction. Ten SCC cases (10/161, 6.2%), and two LCNEC cases (2/31, 6.5%) were positive. Positive cases demonstrated heterogeneous staining of tumor cells, mostly membranous with some cytoplasmic and in one case nuclear pattern. RNA-based sequencing did not demonstrate any NTRK1-3 fusion in our patients' collective. Our study demonstrates that pan-TRK expression in lung carcinoma is very low across different histologic types. NTRK1-3 fusions using an RNA-based sequencing approached could not be detected. This stresses the importance of confirmation of immunohistochemistry results by molecular methods.

Publication types

  • Clinical Trial

MeSH terms

  • Adenocarcinoma of Lung* / enzymology
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / pathology
  • Aged
  • Aged, 80 and over
  • Carcinoma, Neuroendocrine* / enzymology
  • Carcinoma, Neuroendocrine* / genetics
  • Carcinoma, Neuroendocrine* / pathology
  • Carcinoma, Squamous Cell* / enzymology
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms* / enzymology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion* / genetics
  • Oncogene Proteins, Fusion* / metabolism
  • Receptor Protein-Tyrosine Kinases* / genetics
  • Receptor Protein-Tyrosine Kinases* / metabolism
  • Retrospective Studies

Substances

  • Oncogene Proteins, Fusion
  • Receptor Protein-Tyrosine Kinases