Liu Fang-fang, Wei Jia, Lang Rong-gang, Fan Yu, Cui Li-fang, Gu Feng, Fu Li
Department of Breast Pathology and Research Laboratory, Cancer Hospita1 of Tianjin Medical University, Tianjin 300060, China.
Zhonghua Bing Li Xue Za Zhi. 2008 Aug;37(8):529-35.
To study the expression of stromal cell derived factor 1(SDF-1)/CXCR4 and their association with clinicopathologic features and lymph node metastasis in invasive breast carcinoma.
The expression of SDF-1 was studied by immunohistochemistry and in-situ hybridization. Immunohistochemical study for CXCR4 was also performed. The correlation with various clinicopathologic parameters was analyzed.
(1) SDF-1 was mainly expressed in tumor cells and the level of its expression (both membranous and cytoplasmic) in lymph node-positive group was higher than that in lymph node-negative group (P = 0.033). Only cytoplasmic expression correlated with the number of positive lymph node involved by metastasis, TNM tumor stage, histologic grade, tumor dimension and estrogen receptor status (P < 0.05). (2) SDF-1 protein was also detected in the endothelial cells, although its mRNA was rarely detected. SDF-1 staining in lymphatics was associated with positive lymph node (P = 0.005) and SDF-1 staining in blood vessels correlated with stromal lymphocytic reaction (P = 0.001). The extent of nodal involvement was higher in the group with positive SDF-1 staining in blood vessels and with prominent lymphocytic reaction than that in other groups with one or neither of the two features (P < 0.05). (3) On the other hand, CXCR4 was mainly expressed in tumor cells (both nuclear and cytoplasmic); and the level of its expression in lymph node-positive group was higher than that in lymph node-negative group (P = 0.005). Only cytoplasmic expression correlated with the number of positive lymph node involved by metastasis, TNM tumor stage, histologic grade, tumor dimension and HER2 status (P < 0.05). The nuclear expression of CXCR4 was only correlated with progesterone receptor status (P < 0.01). The cytoplasmic expression CXCR4 also positively correlated with SDF-1 expression (P = 0.001).
SDF-1 and CXCR4 can serve as biomarkers for diagnosis and prediction of lymph node metastasis, as well as potential therapeutic targets in invasive breast carcinoma. The difference in localization and staining patterns may also carry different significance.
研究基质细胞衍生因子1（SDF-1）/CXCR4在浸润性乳腺癌中的表达及其与临床病理特征和淋巴结转移的关系。
采用免疫组织化学和原位杂交法研究SDF-1的表达。同时进行CXCR4的免疫组织化学研究。分析其与各种临床病理参数的相关性。
（1）SDF-1主要表达于肿瘤细胞，其在淋巴结阳性组的表达水平（膜性和胞质）高于淋巴结阴性组（P = 0.033）。仅胞质表达与转移累及的阳性淋巴结数目、TNM肿瘤分期、组织学分级、肿瘤大小及雌激素受体状态相关（P < 0.05）。（2）虽然很少检测到SDF-1的mRNA，但在内皮细胞中也检测到了SDF-1蛋白。淋巴管中SDF-1染色与阳性淋巴结相关（P = 0.005），血管中SDF-1染色与间质淋巴细胞反应相关（P = 0.001）。血管中SDF-1染色阳性且有明显淋巴细胞反应的组，其淋巴结受累程度高于其他具有其中一项或两项特征均无的组（P < 0.05）。（3）另一方面，CXCR4主要表达于肿瘤细胞（核性和胞质性）；其在淋巴结阳性组的表达水平高于淋巴结阴性组（P = 0.005）。仅胞质表达与转移累及的阳性淋巴结数目、TNM肿瘤分期、组织学分级、肿瘤大小及HER2状态相关（P < 0.05）。CXCR4的核表达仅与孕激素受体状态相关（P < 0.01）。CXCR4的胞质表达也与SDF-1表达呈正相关（P = 0.001）。
SDF-1和CXCR4可作为浸润性乳腺癌诊断和预测淋巴结转移的生物标志物，以及潜在的治疗靶点。其定位和染色模式的差异可能也具有不同的意义。
