Flt-4-positive vessel density correlates with vascular endothelial growth factor-d expression, nodal status, and prognosis in breast cancer.
Flt-4-positive vessel density correlates with vascular endothelial growth factor-d expression, nodal status, and prognosis in breast cancer.
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发表时间：
2003-11
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通讯作者：
Yasushi Nakamura;H. Yasuoka;M. Tsujimoto;Qifeng Yang;S. Imabun;M. Nakahara;K. Nakao;Misa Nakamura;I. Mori;K. Kakudo
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作者：
Yasushi Nakamura;H. Yasuoka;M. Tsujimoto;Qifeng Yang;S. Imabun;M. Nakahara;K. Nakao;Misa Nakamura;I. Mori;K. Kakudo
目的通过淋巴管转移到区域淋巴结是癌症进展的常见步骤，也是许多类型癌症的重要预后因素。最近的证据表明，肿瘤淋巴管生成促进淋巴转移，并且肿瘤血管和淋巴管上Flt-4的存在可能在介导淋巴管生成因子诱导的新生血管中起重要作用。我们评估了乳腺癌中flt-4阳性血管密度（FVD），并检查FVD是否与淋巴结转移、VEGF-D表达或预后相关。实验设计103浸润性乳腺癌与长期随访纳入我们的研究。采用免疫组化法检测Flt-4的表达，分析FVD与淋巴结转移、VEGF-D表达及其他临床病理参数的关系。并探讨FVD与预后的关系。结果：每例病例的“热点”平均FVD为29.3 ± 22.5。FVD与淋巴结转移（P < 0.0001）、VEGF-D表达（P = 0.0019）、肿瘤大小（P = 0.0015）、雌激素受体（P = 0.0211）、孕激素受体（P = 0.0462）和c-erbB-2（P = 0.0326）显著相关。Kaplan-Meier法和单变量分析确定的生存曲线表明，高FVD与无病生存期（P = 0.0035）和总生存期（P = 0.0336）均相关。结论FVD增高与淋巴结转移和VEGF-D表达有关。高FVD可能是乳腺癌长期生存的一个重要的不利预后因素。Flt-4有可能成为乳腺癌抗血管生成治疗的靶点。
PURPOSE Metastasis to the regional lymph nodes through the lymphatic vessels is a common step in the progression of cancer and an important prognostic factor in many types of cancer. Recent evidence suggests that tumor lymphangiogenesis promotes lymphatic metastasis, and that the presence of Flt-4 on tumor blood and lymphatic vessels may play a important role in mediating lymphangiogenic factor-induced neovascularization. We assessed flt-4-positive vessel density (FVD) in breast cancer, and examined whether FVD associates with lymph node metastasis, VEGF-D expression, or prognosis. EXPERIMENTAL DESIGN One hundred three invasive breast carcinomas with long-term follow-up were included in our study. Flt-4 was assessed using immunohistochemistry, then we analyzed the relationship between FVD and lymph node status, as well as VEGF-D expression and other established clinicopathological parameters. The relationship between FVD and prognosis was also investigated. RESULTS Mean FVD of "hot spot" was 29.3 +/- 22.5 for each case. FVD was correlated significantly with lymph node metastasis (P < 0.0001), VEGF-D expression (P = 0.0019), tumor size (P = 0.0015), estrogen receptor (P = 0.0211), progesterone receptor (P = 0.0462), and c-erbB-2 (P = 0.0326). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high FVD was associated with both worse disease-free survival (P = 0.0035) and overall survival (P = 0.0336). CONCLUSIONS Increased FVD was correlated with lymph node metastasis and VEGF-D expression. High FVD may be a significant unfavorable prognostic factor for long-term survival in breast cancer. It is possible that Flt-4 becomes a target for antiangiogenic therapy to breast cancer.