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The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study

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Summary

The chemokine receptor CXCR4 is an important factor in the migration, invasiveness, metastasis and proliferation of breast cancer cells. We have retrospectively analyzed the levels of expression of CXCR4 in a large cohort of breast cancers and pre-invasive breast samples linked to clinical data. A total of 1808 invasive breast carcinomas and 214 pre-invasive breast samples could be analyzed in correlation with basic clinico-pathological data such as hormone receptor status, HER2 status and tumor grade. The majority of breast cancers expressed either nuclear or cytoplasmic staining or both. CXCR4 cytoplasmic expression was associated with parameters of tumor aggressivity (tumor grade and lymph node status) and had prognostic value (age-adjusted hazard ratio=1.73; Confidence Interval: 1.07–2.77) with respect to disease-specific survival. CXCR4 positivity in the cytoplasm but not the nucleus was associated with HER2 expression and amplification as well as with hormone receptor negativity (both ER and PR). The percentage of nuclear staining increased from normal breast tissue (20%) to ductal carcinoma-in-situ DCIS (43%) to invasive cancer (67%) while CXCR4 was expressed in the cytoplasm of 67% of (DCIS) cases (double that in normal breast samples), suggesting an important role in breast tumor progression. The CXCR4 receptor is expressed in many breast cancers, justifying its development as a therapeutic target in breast cancer patients. Its cytoplasmic expression is associated with breast tumor progression, suggesting potential value as a diagnostic marker.

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Acknowledgements

We thank Giovanna Tosato and Louise Quenneville for helpful discussions, Rosanna Nano and Lucy Sierra for technical assistance. Support from Canadian Breast Cancer Research Alliance, Canadian Institutes of Health Research and Quebec Breast Cancer Foundation.

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Authors and Affiliations

  1. Department of Biomedical Sciences and Biotechnology, Division of Human Anatomy, University of Brescia, Brescia, Italy

    Ombretta Salvucci & Rosella Bianchi

  2. Lady Davis Institute for Medical Research, McGill University, Montreal, Canada

    Amélie Bouchard & Mark Basik

  3. EPOCA Research Center for Occupational, Clinical and Environmental Epidemiology, University of Milan, Milano, Italy

    Andrea Baccarelli

  4. Service d’Anatomopathologie et cytologie, Hôpital Saint-Sacrement, Québec, Canada

    Jean Deschenes

  5. Department of Pathology, Eppendorf University, Hamburg, Germany

    Guido Sauter & Ronald Simon

  6. Department of Pathology, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste Catherine Road, H3T 1E2, Montreal, Quebec, Canada

    Mark Basik

Authors
  1. Ombretta Salvucci
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  2. Amélie Bouchard
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  3. Andrea Baccarelli
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  4. Jean Deschenes
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  5. Guido Sauter
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  6. Ronald Simon
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  7. Rosella Bianchi
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  8. Mark Basik
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Correspondence to Mark Basik.

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Salvucci, O., Bouchard, A., Baccarelli, A. et al. The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study. Breast Cancer Res Treat 97, 275–283 (2006). https://doi.org/10.1007/s10549-005-9121-8

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  • DOI: https://doi.org/10.1007/s10549-005-9121-8

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