Chemokine receptors in advanced breast cancer: differential expression in metastatic disease sites with diagnostic and therapeutic implications
Chemokine receptors in advanced breast cancer: differential expression in metastatic disease sites with diagnostic and therapeutic implications
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DOI：
10.1093/annonc/mdn740
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发表时间：
2009-06-01
影响因子：
50.5
通讯作者：
Cristofanilli, M.
中科院分区：
文献类型：
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作者：
Cabioglu, N.;Sahin, A. A.;Cristofanilli, M.
背景：我们研究了CXCR4、CCR7、雌激素受体(ER)、孕激素受体(PR)和HER2-neu在转移性乳腺癌中的表达，以确定这些生物标志物是否在任何器官特异性转移中优先表达。材料和方法：采用免疫组织化学方法检测41例转移性乳腺癌(n=41)石蜡切片中CXCR4、CCR7、ER、PR和HER2-neu的表达水平。结果：转移性乳腺癌的转移部位包括：骨15例，脑14例，肺6例，肝2例。大网膜转移2例。CXCR4阳性率为41%，CCR7阳性率为10%，HER2-neu阳性率为27%。CXCR4在骨转移癌中的表达高于内脏转移癌(67%vs26%，P=0.020)。内脏部位的CXCR4阳性率较低(肺和脑转移分别为33%和23%)。同样，CCR7基因在骨转移瘤中的表达高于内脏部位(27%vs0%，P=0.037)。结论：CXCR4基因有助于乳腺癌细胞向骨的归巢。这一发现可能具有重要的临床意义，因为转移性骨病患者可能从CXCR4靶向治疗中获得最大好处。
Background: We investigated the expression of CXCR4, CCR7, estrogen receptor (ER), progesterone receptor (PR) and HER2-neu in human metastatic breast cancers to determine whether these biological biomarkers were preferentially expressed in any organ-specific metastases.Materials and methods: CXCR4, CCR7, ER, PR and HER2-neu expression levels were evaluated by immunohistochemical staining using paraffin-embedded tissue sections of metastatic breast cancers (n = 41) obtained by either diagnostic biopsy or surgical resection.Results: The metastatic sites included the following: bone (n = 15), brain (n = 14), lung (n = 6), liver (n = 2), and omental metastases (n = 2). CXCR4 was expressed in 41% of cases, CCR7 expression was demonstrated in 10%, and HER2-neu overexpression was present in 27%. CXCR4 was more likely to be expressed in bone metastases than visceral metastases (67% versus 26%, P = 0.020). Visceral sites demonstrated a lower rate of CXCR4 positivity (33% and 23%, respectively, for lung and brain metastases). Similarly, CCR7 was more likely to be found in bone metastases than visceral sites (27% versus 0%, P = 0.037).Conclusions: These results indicate that CXCR4 can contribute to the homing of breast cancer cells to the bone. This finding might have important clinical implications since patients with metastatic bone disease may achieve the highest benefit from a CXCR4-targeted therapy.