Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma

Qiqi Ye; Hui Chen; Cody Han; Yan Peng; Xiao Huang; Hongxia Sun; Yun Wu; Constance T Albarracin; Lavinia P Middleton; Aysegul A Sahin; Lei Huo; Qingqing Ding

doi:10.1136/jcp-2023-208989

Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma

J Clin Pathol. 2023 Aug 16:jcp-2023-208989. doi: 10.1136/jcp-2023-208989. Online ahead of print.

Authors

Affiliations

¹ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
² Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
³ Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA qqding@mdanderson.org.

PMID: 37586834
DOI: 10.1136/jcp-2023-208989

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.

Keywords: Biomarkers, Tumor; Breast Neoplasms; IMMUNOHISTOCHEMISTRY.