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Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma
  1. Qiqi Ye1,
  2. Hui Chen1,
  3. Cody Han1,
  4. Yan Peng2,
  5. Xiao Huang3,
  6. Hongxia Sun1,
  7. Yun Wu1,
  8. Constance T Albarracin1,
  9. Lavinia P Middleton1,
  10. Aysegul A Sahin1,
  11. Lei Huo1,
  12. Qingqing Ding1
  1. 1 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2 Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
  3. 3 Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  1. Correspondence to Qingqing Ding; qqding{at}mdanderson.org

Abstract

Aims Secretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was previously found in 10% of non-secretory breast carcinomas. To further examine pan-Trk IHC specificity, we evaluated pan-Trk staining in various breast carcinoma subtypes.

Methods The study cohort consisted of 346 invasive breast carcinomas (IBCs), including 8 SCBs and 48 triple-negative histological mimickers (36 metaplastic carcinomas, including 12 matrix-producing carcinomas; 5 adenoid cystic carcinomas; 5 apocrine carcinomas; 2 acinic cell carcinomas), 101 triple-negative IBCs of no special type, 101 estrogen receptor (ER)-positive/HER2-negative IBCs and 88 HER2-positive IBCs. Six salivary gland secretory carcinomas were also included. Pan-Trk IHC was performed on tumours using a rabbit monoclonal pan-Trk antibody. Any nuclear staining in the invasive carcinoma cells was considered positive.

Results All 14 secretory carcinomas from breast and salivary gland exhibited moderate to strong pan-Trk nuclear staining. In contrast, no pan-Trk nuclear staining was identified in any of the 338 non-secretory IBCs. Focal cytoplasmic pan-Trk staining was observed in nine non-secretory IBCs (2.7%), and was considered nonspecific and negative.

Conclusions Our results indicate that pan-Trk nuclear staining is highly specific for SCB. In low-grade to intermediate-grade IBCs that share histological features with SCB, adding pan-Trk to a routing panel of estrogen receptor/progesterone receptor/HER2 is highly diagnostic. Our results also support using pan-Trk IHC to differentiate SCB from its triple-negative histological mimickers, such as adenoid cystic carcinoma, matrix-producing carcinoma, apocrine carcinoma and acinic cell carcinoma.

  • IMMUNOHISTOCHEMISTRY
  • Breast Neoplasms
  • Biomarkers, Tumor

Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.

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Data availability statement

Data sharing not applicable as no datasets generated and/or analysed for this study.

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Footnotes

  • Handling editor L C Collins.

  • Contributors QY, LH and QD performed study concept and design and writing; QY, HC, CH, YP, XH, HS, YW, CTA, LPM, LH and QD performed experiments, data collection and analysis; QY, HC, CH, YP, XH, HS, YW, CTA, LPM, LH and QD provided analysis and interpretation of data and review and revision of the manuscript. All authors read and approved the revised version of the manuscript. QD and LH are guarantor.

  • Funding This study was supported by MD Anderson Department of Pathology faculty grant and Division of Pathology and Laboratory Medicine research fund to QD.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.