TRK EDUCATION

Stains

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Pan-TRK (EPR17341) [NTRK]

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Features

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• Expressed in tumors harboring NTRK1/2/3 gene fusions

• High sensitivity and specificity ranging from 95 - 100% and 92 - 100%, respectively (Am J Surg Pathol 2017;41:1547, Am J Surg Pathol 2018;42:927, Histopathology 2018;73:634)

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Pathophysiology​

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• NTRK gene fusions (NTRK1/2/3) to a variety of gene partners are oncogenic drivers in several tumor types

• In some tumor morphologies, NTRK fusions occur at a high frequency:

  • Infantile fibrosarcoma and other pediatric NTRK rearranged mesenchymal tumors

  • Cellular congenital mesoblastic nephroma

  • Secretory carcinomas (breast, salivary gland mammary analog secretory carcinoma and skin)

  • Lipofibromatosis-like neural tumor

  • Uterine sarcomas with NTRK fusions resembling fibromatosis

• In some pediatric tumors, NTRK fusions occur with intermediate frequency:

  • Pediatric gliomas, pediatric papillary thyroid carcinoma, Spitz nevi

• In other tumors, NTRK fusions occur very infrequently:

  • Adult gliomas, adult papillary thyroid carcinoma, colorectal carcinoma, lung adenocarcinoma, melanoma, leukemia and less commonly others

• Recognition of NTRK fusion tumors had become increasingly important with the advent of targeted Trk inhibitors

• Tumors harboring NTRK1/2 fusions demonstrate cytoplasmic expression; rare perinuclear and nuclear membrane staining has been reported

• Tumors harboring NTRK3 fusions demonstrate cytoplasmic or nuclear expression