High expression of the chemokine receptor CCR7 is associated with worse outcome in breast cancer

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9593 Background: Breast cancers can express chemokine receptors to varying degrees, notably CCR7 and CXCR4, whereas their ligands can be expressed on organs that represent important sites of breast cancer metastasis. These findings have implicated chemokines and their receptors in directing breast cancer cells to specific sites of metastasis. Using a breast cancer tissue microarray (TMA), we analyzed the protein expression and sub-cellular localization of CCR7 and CXCR4. Methods: Our TMA consisted of 659 cases of primary breast cancers, nearly equally divided between node negative and node positive cancers. We used our automated quantitative image analysis software (AQUA), which uses a modified immuno-histochemistry technique with fluorochromes as a detection method. Primary antibodies were monoclonal CCR7 (BD Pharmagin, Minneapolis, MN) and CXCR4 (R&D Systems, Minneapolis, MN). All statistical analyses were performed using Statview software (version 5.0.1; SAS Institute Inc., Cary, NC). The total tumor and sub-cellular distribution pattern of CCR7 and CXCR4 were then correlated with clinico-pathologic factors and outcome. Results: CCR7 stained predominantly in a membrane/cytoplasmic distribution, whereas CXCR4 stained more diffusely throughout the entire tumor. We chose to divide the AQUA continuous data into traditional quartiles. This showed that the highest 25% of CCR7 expressers had a worse disease-specific survival when compared to the lowest 25% expressers (p=0.03). No significant correlation was identified between CCR7 expression and ER/PR, HER2/neu, nodal status, tumor size or nuclear grade. CXRC4 expression within the entire tumor or within the subcellular compartments was not associated with any of the clinico-pathologic variables or clinical outcomes. Conclusions: CCR7 and CXCR4 are variably expressed in breast cancers. Highest expression of the chemokine receptor CCR7 correlates with poor survival, without significant correlation with other clinico-pathologic factors. No significant financial relationships to disclose.