The dissemination of breast carcinoma cell outside the organ of origin involves multiple steps, e.g. loss or deregulation of normal cell-cell contacts, production of enzyme remodelling the extracellular matrix, production of motility factors and acquisition of migration capacities. Several studies have reported that chemokines and their receptors can be expressed by epithelial tumor cells and may contribute to cell migration [5, 7–11].
The objective of the present study was to investigate the presence of CCR6 and CCR7 chemokine receptors and their ligands in non-metastatic primary breast carcinomas. CCR6 and CCR7 were chosen because they are physiologically involved in the migration of immune cells to peripheral tissues and lymph nodes respectively. Expression of these chemokine and chemokine receptors was assessed using IHC. CCR6, CCR7 and CCL19 were found to be expressed in a large proportion of tumors and were, in most cases, associated with features of more aggressive disease, such as higher histological grade and HER2 overexpression. We could not detect any CCL20 expression in our series using IHC on paraffin embedded tissue sample while we were previously able to show CCL20 expression on frozen tissue section , using a different antibody. Lack of CCL20 detection in our series may therefore be regarded as a technical limitation. CCL21 was expressed at low levels in very few tumors in this series. Further studies, using different techniques such as quantitative RT-PCR or protein extraction on frozen samples, will be needed to accurately assess the expression of CCL20 and CCL21 in primary breast cancer. CCR6 was detectable in tumor cells, while CCL19 was expressed by both tumor cells and stroma-infiltrating cells exhibiting a dendritic morphology. In this series CCR7 was found to be expressed only on stromal cells either with myofibroblastic morphology and α-SMA expression or with dendritic morphology, but not on tumor cells. In previously reported series, CCR7 expression had been described on tumor cells from breast cancer [7, 8] as well as from other tumors such as gastric and lung cancer [11, 19] but not on cells in the tumor stroma. The reasons for this discrepancy are not clear, and may possibly reflect different methods used for IHC staining. Indeed, André et al  and Cabioglu et al  both used the same anti-CCR7 antibody, but with different peroxydase bloking agents and different antibody incubation time. (Cabioglu et al 2005  and F. André, personal communication). The precise nature of these CCR7-expressing cells remains unclear. Despite the fact that CCR7 was found on stromal cells in the present study this feature was still significantly associated with node involvement. However, unlike what was previously reported and despite the fact the CCR7-expression on stromal cells was associated with several features of aggressive disease, we were unable to show any correlation between CCR7 expression and poorer outcome whether in univariate or multivariate analysis. This finding also raises concerns on the consistency and interpretation of IHC studies and therefore on the role of IHC in the identification of biomarkers.
CCR6 was expressed on tumor cells and its expression was associated with shorter relapse-free survival in univariate but not in multivariate analysis, and its impact on overall survival was not statistically significant. Although CCR6 expression has been reported in several cancers and usually correlates with more aggressive disease [20, 21, 27], it's association with shorter RFS has never been demonstrated before. CCR6 may increase tumor cells' motility and therefore their metastatic potential by acting on the cytoskeleton, as has been described in a model of colonic epithelium .
We also found that tumor infiltration by CCL19-expressing DC was associated with shorter relapse-free survival in both univariate and multivariate analysis. However since mature DCs are known to express both CCR7 and CCL19  the patho-physiological meaning of this finding is unclear. Indeed since we did not use other markers of DC, this finding may reflect the fact that tumor infiltration by DC is of poor prognosis as suggested in a previous report.
Finally, we found that CCR7-expressing stromal cells were also present in lymph nodes invaded by tumor cells but this finding was restricted to the patients who had CCR7-expressing stromal cells in their primary tumor. This finding suggests that tumor cells may be able to recruit CCR7-expressing stromal cells.