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

Abstract

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.

Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft‐tissue sarcoma

“…Some investigators have demonstrated that CXCR4 is highly expressed in tumor tissue compared with its corresponding normal tissue. 1,24,25 In the current study, the level of CXCR4 mRNA in tumor tissue was significantly higher than that of normal skeletal muscle tissue, which was used as a non-tumorous reference. Among the different types of tumor tissue, however, the CXCR4 expression level of MRCT was lower than that of intermediate tumor or MNRCT.…”

Negative regulation of chemokine receptor CXCR4 by tumor suppressor p53 in breast cancer cells: implications of p53 mutation or isoform expression on breast cancer cell invasion

“…Because CXCR4 overexpression and p53 mutations are common in cancers, our study suggests a link between these two major signaling pathways involved in cancer progression (Vousden and Lu, 2002;Balkwill, 2004). In breast cancer, CXCR4 expression increases progressively with increasing malignant potential and higher expression is associated with lymph node positivity, hormone receptor negativity, Her2 overexpression and poor survival (Cabioglu et al, 2005;Salvucci et al, 2005). These studies, however, did not compare CXCR4 expression with p53 status.…”

Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells

“…Several clinical studies have recently examined increased expression of CXCR4 as a possible predictor of mammary carcinoma metastasis (Salvucci et al, 2006). Detection of an increase in CXCR4 requires a large tissue sample for immunohistochemical or mRNA expression analysis and need for CXCR4 to be increased in a large percentage of the tumor.…”

“…Accordingly, mammary carcinoma cells metastasize primarily to those tissues expressing highest tissue levels of CXCL12 including bone, liver and lung (Muller et al, 2001). Studies suggest that CXCR4 expression on tumor cells correlates with increased metastasis and decreased clinical prognosis (Salvucci et al, 2006). Moreover, blocking CXCR4 inhibits breast cancer cells from metastasizing to organs expressing CXCL12 (Muller et al, 2001;Smith et al, 2004).…”