Pan-TRK immunohistochemistry as a tool in the screening for NTRK gene fusions in cancer patients

Abstract

Therapy with TRK inhibitors is a tumor-agnostic treatment directed against specific molecular changes rather than cancer type. NTRK fusions are rare in most prevalent cancers, accounting for less than 0.5% of cases. However, there is a group of rare cancers in which NTRK fusion is more prevalent. These include secretory carcinoma of the breast and salivary gland, childhood sarcomas, such as infantile fibrosarcoma, and cellular and mixed congenital mesoblastic nephroblastoma. The most common rearrangement pertains to NTRK3 and the most common fusion gene is ETV6. Identifying patients with NTRK gene fusions who would likely benefit from targeted therapy with TRK inhibitors requires practical diagnostic tools and an appropriate management strategy of diagnostic trajectory. The fusions can be detected by molecular biology techniques or pan-TRK immunohistochemistry. The latter detects NTRK1/2/3 gene fusions independently of the resulting fusion gene but does not determine which of them has been rearranged or what the fusion partner is. The sensitivity and specificity of the method reach 97% and 100%, respectively. Other advantages include the relatively low cost, short duration of examination, and broad accessibility of immunohistochemistry laboratories. These characteristics make this method a useful screening tool for detecting patients with NTRK gene fusions.