CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients

BACKGROUND: The CXC chemokine receptor (CXCR) 7 is involved in tumour development and metastases formation. The aim of the present study was to determine protein expression of CXCR7, its putative co-receptors epidermal growth factor receptor (EGFR) and CXCR4, its predominant ligand CXCL12, their co-dependency and their association with survival in cervical cancer patients. METHODS: CXC chemokine receptor 7, EGFR, CXCR4 and CXCL12 expression were determined immunohistochemically in 103 paraffin-embedded, cervical cancers. Subsequently, associations with patient characteristics were assessed and survival analyses were performed. RESULTS: CXC chemokine receptor 7 was expressed by 43% of tumour specimens, in a large majority of cases together with either EGFR or CXCR4 (double positive), or both (triple positive). The CXCR7 expression was associated with tumour size (P = 0.013), lymph node metastasis (P = 0.001) and EGFR expression (P = 0.009). CXC chemokine receptor 7 was independently associated with disease-free survival (hazard ratio (HR) = 4.3, 95% confidence intervals (CI) 1.7-11.0, P = 0.002), and strongly associated with disease-specific survival (HR = 3.9, 95% CI 1.5-10.2, P = 0.005). CONCLUSION: CXC chemokine receptor 7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients, and might be a promising new therapeutic marker. In a large majority of cases, CXCR7 is co-expressed with CXCR4 and/or EGFR, supporting the hypothesis that these receptors assist in CXCR7 signal transduction. British Journal of Cancer (2012) 106, 1520-1525. doi:10.1038/bjc.2012.110 www.bjcancer.com (C) 2012 Cancer Research UK