Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors

Erin R. Rudzinski, Christina M. Lockwood, Bradley A. Stohr, Sara O. Vargas, Rachel Sheridan, Jennifer O. Black, Veena Rajaram, Theodore W. Laetsch, Jessica Davis

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Activating neurotrophic receptor kinase (NTRK) fusions define certain pediatric mesenchymal tumors, including infantile fibrosarcoma and cellular mesoblastic nephroma. Traditionally, molecular confirmation of these fusions has included either fluorescent in situ hybridization for ETV6 rearrangements or reverse-transcriptase polymerase chain reaction for the classic ETV6-NTRK3 fusion. However, these methods overlook variant NTRK rearrangements, which are increasingly appreciated as recurrent events in a subset of pediatric mesenchymal tumors. New therapeutic agents successfully target these fusions and may prevent morbid surgeries in very young children, making recognition of tumors harboring NTRK rearrangements of increasing importance. We evaluated the performance of immunohistochemical (IHC) staining using pan-Trk and TrkA antibodies in 79 pediatric mesenchymal tumors. Negative controls included pediatric mesenchymal tumors not harboring (n=28) or not expected to harbor (n=22) NTRK fusions. NTRK rearrangements were detected predominantly by DNA-based next-generation sequencing assays, specifically UW OncoPlex and UCSF500 Cancer Gene Panel. Pan-Trk IHC (EPR17341) was 97% sensitive and 98% specific for the presence of an NTRK rearrangement, and TrkA IHC (EP1058Y) was 100% sensitive and 63% specific for the presence of an NTRK rearrangement. Tumors with NTRK1 or NTRK2 rearrangements showed cytoplasmic staining, whereas tumors with NTRK3 rearrangements showed nuclear +/- cytoplasmic staining. We conclude that pan-Trk IHC is a highly sensitive and specific marker for NTRK rearrangements in pediatric mesenchymal tumors.

Original languageEnglish (US)
Pages (from-to)927-935
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume42
Issue number7
DOIs
StatePublished - Jan 1 2018

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Phosphotransferases
Immunohistochemistry
Pediatrics
Neoplasms
Staining and Labeling
Mesoblastic Nephroma
Fibrosarcoma
Neoplasm Genes
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Antibodies
DNA

Keywords

  • immunohistochemistry
  • NTRK
  • pediatric
  • soft tissue sarcoma
  • Trk

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. / Rudzinski, Erin R.; Lockwood, Christina M.; Stohr, Bradley A.; Vargas, Sara O.; Sheridan, Rachel; Black, Jennifer O.; Rajaram, Veena; Laetsch, Theodore W.; Davis, Jessica.

In: American Journal of Surgical Pathology, Vol. 42, No. 7, 01.01.2018, p. 927-935.

Research output: Contribution to journalArticle

Rudzinski, ER, Lockwood, CM, Stohr, BA, Vargas, SO, Sheridan, R, Black, JO, Rajaram, V, Laetsch, TW & Davis, J 2018, 'Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors', American Journal of Surgical Pathology, vol. 42, no. 7, pp. 927-935. https://doi.org/10.1097/PAS.0000000000001062
Rudzinski, Erin R. ; Lockwood, Christina M. ; Stohr, Bradley A. ; Vargas, Sara O. ; Sheridan, Rachel ; Black, Jennifer O. ; Rajaram, Veena ; Laetsch, Theodore W. ; Davis, Jessica. / Pan-Trk Immunohistochemistry Identifies NTRK Rearrangements in Pediatric Mesenchymal Tumors. In: American Journal of Surgical Pathology. 2018 ; Vol. 42, No. 7. pp. 927-935.
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