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Open Access Research article

Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

Philippe A Cassier12*, Isabelle Treilleux3, Thomas Bachelot12, Isabelle Ray-Coquard1, Nathalie Bendriss-Vermare2, Christine Ménétrier-Caux2, Olivier Trédan1, Sophie Goddard-Léon3, Jean-Jacques Pin4, Hervé Mignotte5, Clarisse Bathélémy-Dubois6, Christophe Caux2, Serge Lebecque4 and Jean-Yves Blay124*

Author Affiliations

1 Departments of Medecine, Centre Léon Bérard, Lyon, France

2 Equipe Cytokine et Cancer, INSERM U590, Centre Léon Bérard, Lyon, France

3 Departments of Pathology, Centre Léon Bérard, Lyon, France

4 Université Claude Bernard Lyon 1, Lyon, France

5 Departments of Surgery, Centre Léon Bérard, Lyon, France

6 Innate Pharma, Marseille, France

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BMC Cancer 2011, 11:213  doi:10.1186/1471-2407-11-213

Published: 30 May 2011

Abstract

Background

Chemokines and chemokine receptors are major actors of leukocytes trafficking and some have been shown to play an important role in cancer metastasis. Chemokines CCL19, CCL20 and CCL21 and their receptors CCR6 and CCR7, were assessed as potential biomarkers of metastatic dissemination in primary breast cancer.

Methods

Biomarker expression levels were evaluated using immunohistochemistry on paraffin-embedded tissue sections of breast cancer (n = 207).

Results

CCR6 was expressed by tumor cells in 35% of cases. CCR7 was expressed by spindle shaped stromal cells in 43% of cases but not by tumor cells in this series. CCL19 was the only chemokine found expressed in a significant number of breast cancers and was expressed by both tumor cells and dendritic cells (DC). CCR6, CCL19 and CCR7 expression correlated with histologic features of aggressive disease. CCR6 expression was associated with shorter relapse-free survival (RFS) in univariate and but not in multivariate analysis (p = 0.0316 and 0.055 respectively), and was not associated with shorter overall survival (OS). Expression of CCR7 was not significantly associated with shorter RFS or OS. The presence of CCL19-expressing DC was associated with shorter RFS in univariate and multivariate analysis (p = 0.042 and 0.020 respectively) but not with shorter OS.

Conclusion

These results suggest a contribution of CCR6 expression on tumor cells and CCL19-expressing DC in breast cancer dissemination. In our series, unlike what was previously published, CCR7 was exclusively expressed on stromal cells and was not associated with survival.

Keywords:
early breast cancer; chemokine; chemokine receptor; prognosis; metastasis