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.