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Impact of NOTCH1 expression in primary breast adenoid cystic carcinoma
  1. Alireza Salem1,2,
  2. Yun Wu1,
  3. Qingqing Ding1,
  4. Lavinia P Middleton1
  1. 1Pathology, The University of Texas, Houston, Texas, USA
  2. 2Columbia University Medical Center, New York, New York, USA
  1. Correspondence to Dr Alireza Salem, Pathology, Columbia University Medical Center, 622 West 168th Street VC14-215C 10032 New York, New York, USA; as7027{at}cumc.columbia.edu

Abstract

Aims Adenoid cystic carcinoma (AdCC) originates from salivary-type like glands in the head and neck, lung, and breast. AdCC shows chromosomal translocation, resulting in MYB::NFIB fusion and overexpression of MYB. Recently, NOTCH1 pathway alteration has been recognised in a subset of patients with salivary gland AdCC and has been shown to be associated with poor survival. In this study, we investigated the correlation of NOTCH1 pathway alteration with the clinical outcome of patients with primary breast AdCC by examining NOTCH1 immunoreactivity in attempts to better predict clinical outcomes.

Methods We identified 25 cases of breast AdCC, reviewed the clinical outcome and performed immunohistochemical (IHC) staining for NOTCH1 on FFPE sections.

Results IHC evaluation of NOTCH1 expression in 25 cases of primary breast AdCCs revealed a positive correlation between NOTCH1 expression and primary tumour size. All cases with NOTCH1 expression were greater than 15 mm in size at presentation but only 50% of NOTCH1 negative tumours were greater than 15 mm. We demonstrated a positive correlation between NOTCH1 positive AdCCs and recurrence/metastases. 63.6% of NOTCH1 positive AdCCs had either metastases or recurrence. On the contrary, only 21.5% of NOTCH1 negative AdCCs had recurrence or metastases. AdCCs with NOTCH1 positivity correlated with inferior relapse free survival (median 33 vs 129 months).

Conclusions Our study demonstrates that in patients with breast AdCC, overexpression of NOTCH1 ≥20% is associated with larger tumour size and aggressive clinical outcomes. Importantly, NOTCH1 inhibitors may have potential therapeutic effect in patients with breast AdCC.

  • BREAST
  • Breast Neoplasms
  • Pathology, Surgical

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Handling editor L C Collins.

  • Twitter @Alirezasalem2

  • Contributors AS and LPM contributed to planning, study proposal, collecting data, writing the manuscript and responsible for the overall content as guarantor. QD and YW contributed as scientific advisors, provide resources and editing manuscript.

  • Funding This work was supported by faculty funds provided by MD Anderson Cancer Center.

  • Competing interests None declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.