Kato Masahiro, Kitayama Joji, Kazama Shinsuke, Nagawa Hirokazu
Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan.
Breast Cancer Res. 2003;5(5):R144-50. doi: 10.1186/bcr627. Epub 2003 Jul 17.
The stromal cell-derived factor-1/CXC chemokine receptor-4 (SDF-1/CXCR4) signal has been shown to be important in various immunological reactions. Recent studies have suggested that CXCR4 is expressed in certain cancer cells and that they use this chemokine receptor efficiently for metastasis formation.
The expression of CXCR4 was evaluated by immunohistochemical study in 79 surgically resected invasive ductal carcinomas, and the relation between the staining pattern and clinicopathological features was examined.
CXCR4 was diffusely and homogeneously expressed in 59 cancers, which were further divided into 28 high-expression and 31 low-expression cancers by their staining intensity. The other 20 cancers showed heterogeneous immunoreactivity in tumor tissue, which was defined as focal type. In comparison with the diffuse type, focal type tumors showed significantly more extensive lymph node metastasis, because the number and extent of metastatic nodes were larger in the focal than the diffuse type. In the diffuse type, the rate of node-positive cases did not show a difference in staining intensity. However, high-CXCR4 tumors showed more extensive nodal metastasis in comparison with low-expression tumors. In contrast, the expression pattern of CXCR4 did not have a significant correlation with hematogeneous metastasis. The overall survival of these patients tended to be better in the diffuse type than in the focal type, although the difference was not statistically significant.
The expression pattern of CXCR4 was significantly correlated with the degree of lymph node metastasis in breast cancers. Our data suggest that CXCR4 might be particularly important in facilitating metastasis through the lymphatic system.
基质细胞衍生因子-1/CXC趋化因子受体-4(SDF-1/CXCR4)信号在多种免疫反应中已显示出重要作用。最近的研究表明,CXCR4在某些癌细胞中表达,并且它们有效地利用这种趋化因子受体形成转移。
通过免疫组织化学研究评估79例手术切除的浸润性导管癌中CXCR4的表达,并检查染色模式与临床病理特征之间的关系。
CXCR4在59例癌症中呈弥漫性和均匀性表达,根据染色强度进一步分为28例高表达癌和31例低表达癌。另外20例癌症在肿瘤组织中表现出异质性免疫反应,定义为局灶型。与弥漫型相比,局灶型肿瘤显示出明显更广泛的淋巴结转移,因为局灶型转移淋巴结的数量和范围大于弥漫型。在弥漫型中,淋巴结阳性病例的比例在染色强度上没有差异。然而,与低表达肿瘤相比,高CXCR4肿瘤显示出更广泛的淋巴结转移。相反,CXCR4的表达模式与血行转移没有显著相关性。这些患者的总生存期在弥漫型中往往比局灶型更好,尽管差异没有统计学意义。
CXCR4的表达模式与乳腺癌的淋巴结转移程度显著相关。我们的数据表明,CXCR4在促进通过淋巴系统转移方面可能特别重要。