Pan-Trk immunohistochemistry reliably identifies ETV6-NTRK3 fusion in secretory carcinoma of the salivary gland

Virchows Arch. 2020 Feb;476(2):295-305. doi: 10.1007/s00428-019-02640-7. Epub 2019 Aug 19.

Abstract

Secretory carcinoma of the salivary gland is a newly recognized entity that morphologically resembles breast secretory carcinoma and has a characteristic t(12;15)(p13;q25) ETV6-NTRK3 translocation. Fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) analyses can detect the ETV6-NTRK3 fusion; however, both tests are expensive and not widely available. In this study, we aimed to determine whether pan-Trk immunohistochemistry (IHC) could detect ETV6-NTRK3 fusions as reliably as RT-PCR and FISH. We performed pan-Trk IHC in 70 salivary gland cancer samples, including secretory carcinomas, acinic cell carcinomas, and hybrid carcinomas. Nineteen tumors exhibited positive pan-Trk staining, including 16 secretory carcinomas, 2 hybrid carcinomas with a secretory carcinoma component, and 1 acinic cell carcinoma. Pan-Trk IHC staining was localized in the nucleus in 16 (84.2%) cases and in the cytoplasm and/or membrane in 3 (15.8%) cases. RT-PCR analysis for the ETV6-NTRK3 transcript was conducted in 45 samples; the fusion transcript was present in 11 of 12 secretory carcinomas and absent in 32 acinic cell carcinomas and 1 mucoepidermoid carcinoma. Pan-Trk IHC was positive in 10 of 11 salivary tumors that were positive for ETV6-NTRK3 by RT-PCR and negative in all 34 tumors that were negative for the fusion by RT-PCR. Therefore, in comparison with RT-PCR, pan-Trk IHC had a sensitivity of 90.9% and specificity of 100%. In conclusion, our data showed that pan-Trk IHC is a reasonable screening test for diagnosing secretory carcinoma of the salivary gland.

Keywords: ETV6-NTRK3; Fluorescence in situ hybridization; Immunohistochemistry; Salivary gland; Secretory carcinoma.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carcinoma / diagnosis
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Carcinoma, Acinar Cell / genetics
  • Carcinoma, Acinar Cell / pathology
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization, Fluorescence / methods
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism*
  • Proto-Oncogene Proteins c-ets / genetics
  • Repressor Proteins / genetics
  • Salivary Gland Neoplasms / diagnosis
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / pathology*
  • Salivary Glands / metabolism

Substances

  • Biomarkers, Tumor
  • ETV6-NTRK3 fusion protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins

Supplementary concepts

  • Secretory breast carcinoma

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