The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study
- 592 Downloads
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.
Keywordsbreast cancer chemokine receptor CXCR4 ductal carcinoma-in-situ tissue microarray estrogen receptor Her2 prognosis
Unable to display preview. Download preview PDF.
We thank Giovanna Tosato and Louise Quenneville for helpful discussions, Rosanna Nano and Lucy Sierra for technical assistance. Support from Canadian Breast Cancer Research Alliance, Canadian Institutes of Health Research and Quebec Breast Cancer Foundation.
- 12.Press MF, Sauter G, Bernstein L, Villalobos IE, Mirlacher M, Zhou JY, Wardeh R, Li YT, Guzman R, Ma Y, Sullivan-Halley J, Santiago A, Park JM, Riva A, Slamon DJ, Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trialsClin Cancer Res 11(18):6598–6607, 2005CrossRefPubMedGoogle Scholar
- 17.Kang H, Watkins G, Parr C, Douglas-Jones A, Mansel RE, Jiang WG, Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancerBreast Cancer Res 7(4):R402–R410, 2005CrossRefPubMedGoogle Scholar
- 23.Tamamura H, Omagari A, Hiramatsu K, Gotoh K, Kanamoto T, Xu Y, Kodama E, Matsuoka M, Hattori T, Yamamoto N, Nakashima H, Otaka A, et al. Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140Bioorg Med Chem Lett 11: 1897–1902, 2001CrossRefPubMedGoogle Scholar