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Expression of neurotensin receptor-1 (NTS1) in primary breast tumors, cellular distribution, and association with clinical and biological factors

  • Preclinical study
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Abstract

Purpose

Neurotensin receptor-1 (NTS1) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified.

Methods

We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS1 expression and clinical, pathological, and biological parameters, as well as patient outcomes.

Results

Out of 1419 primary breast tumors, moderate to strong positivity for NTS1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main “correlates” of a nuclear location of NTS1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS1-positive samples, cytoplasmic expression of NTS1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS1 nuclear staining. Ancillary analysis showed NTS1 expression in 73% of invaded lymph nodes from NTS1-positive primaries.

Conclusion

NTS1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS1-targeting strategy, including radiopharmaceuticals for imaging and therapy.

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Funding

This work was funded by Institut National du Cancer (INCa PLBIO 2017, THERACAN project) and was achieved within the context of the Laboratory of Excellence TRAIL ANR-10-LABX-57.

Author information

Authors and Affiliations

  1. Nuclear Medicine Department, University Hospital of Bordeaux, 33076, Bordeaux, France

    Clément Morgat, Adrien Chastel & Elif Hindié

  2. University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, 33000, Bordeaux, France

    Clément Morgat, Adrien Chastel & Elif Hindié

  3. Clinical and Epidemiological Research Unit, Institut Bergonié, 33076, Bordeaux, France

    Véronique Brouste

  4. Surgical Pathology Unit, Department of Biopathology, Institut Bergonié, 33076, Bordeaux, France

    Valérie Vélasco & Gaétan Macgrogan

  5. INSERM, ACTION U1218, 33076, Bordeaux, France

    Valérie Vélasco & Gaétan Macgrogan

  6. Institut Universitaire de France (IUF), Paris, France

    Elif Hindié

Authors
  1. Clément Morgat
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  2. Véronique Brouste
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  4. Valérie Vélasco
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  6. Elif Hindié
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Contributions

CM contributes to the conception, acquisition, analysis, interpretation of data, and funding and wrote the manuscript. VB analyzed and interpreted the data and approved the final version of the manuscript. AC contributes to data acquisition and approved the final version of the manuscript. VV acquired the data and approved the final version of the manuscript. GMG acquired and analyzed the data and approved the final version of the manuscript. EH analyzed and interpreted the data, participated in the funding, and approved the final version of the manuscript.

Corresponding author

Correspondence to Clément Morgat.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the IRB of Institut Bergonié (Breast Research Group) who determined that our study did not need ethical approval. An IRB official waiver of ethical approval was granted from the IRB of Institut Bergonié.

Informed consent

The Ethics committee of Institut Bergonié waived requirement for informed consent for the present retrospective analysis.

Cell lines

MCF-7, MDA-MB-453, MDA-MB-468, SKBR3, T47D, and ZR75.1 cell lines were obtained from Dr N. Jones (Univ. Bordeaux, France) and no additional authentication was performed by the authors of this study.

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Morgat, C., Brouste, V., Chastel, A. et al. Expression of neurotensin receptor-1 (NTS1) in primary breast tumors, cellular distribution, and association with clinical and biological factors. Breast Cancer Res Treat 190, 403–413 (2021). https://doi.org/10.1007/s10549-021-06402-5

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