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Is Pan-TRK Immunohistochemistry the Optimal Way to Identify NTRK Gene Fusions in Brain Tumors?

By: Vanessa A. Carter, BS
Posted: Monday, April 25, 2022

Maher Kurdi, MD, of King Abdulaziz University, Rabigh, Saudi Arabia, and colleagues aimed to evaluate whether pan-TRK immunohistochemistry is an efficient and reliable marker for the detection of NTRK fusions in brain tumors. Unfortunately, pan-TRK was not identified as a viable tissue-efficient biomarker for these gene fusions in central nervous system tumors, and these results suggest that next-generation sequencing may have higher specificity over detecting these gene fusions. These findings were published in Pathology and Oncology Research.

“RNA-based next-generation sequencing should be used as an alternative method to detect NTRK fusions,” concluded the study authors. “TruSightOnco500 is a wide-genomic platform that can replace immunohistochemistry and other molecular techniques to screen for DNA and RNA-based mutation using formalin-fixed and paraffin-embedded tissue.”

A total of 23 patients diagnosed with pilocytic astrocytoma (n = 8), IDH wild-type glioblastoma (n = 6), IDH-mutant astrocytoma (n = 4), oligodendroglioma, astroblastoma, central neurocytoma, medulloblastoma, and/or liponeurocytoma (n = 1 each) were enrolled. The monoclonal antibody EPR17341 was used to test for pan-TRK immunohistochemistry on formalin-fixed and paraffin-embedded tissues. NTRK fusions were identified using DNA- and RNA-based next-generation sequencing.

The mean patient age was 35 years, and the cohort included 16 adults and 7 children. Approximately 47.8% (n = 11) of tumors had detectable pan-TRK expression and were further stratified by diffuse expression (n = 4), focal expression (n = 4), and partial expression (n = 3). Interestingly, only two adult cases (glioblastoma, liponeurocytoma) with pan-TRK expression harbored NTRK fusions; all other cases exhibited no NTRK fusions regardless of pan-TRK expression status.

There was no statistically significant correlation between NTRK fusions and pan-TRK expression, suggesting that pan-TRK expression is not always associated with the presence of these gene alterations. Despite a relatively high sensitivity of immunohistochemistry relative to next-generation sequencing, the ability to detect negative pan-TRK expression was 57.1%. Of note, the overall diagnostic accuracy of pan-TRK in detecting NTRK fusions was 60.9%.

Disclosure: The study authors reported no conflicts of interest.

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