HIF-1α和VEGF-C在乳腺癌淋巴管生成中的作用机制

Objective To investigate the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-C (VEGF-C) and the correlations with clinic parameters, and to make sure the effect of DOI:10.3760/cma.j.issn.1673-422X.2013.10. 基金项目：安徽省卫生厅自然科学基金（09C230）作者单位：241000 安徽省芜湖市第二人民医院乳腺外科（赵迎春、朱永云、罗传瑜），病理科（李勇）通信作者：赵迎春，E-mail: lcy0508@hotmail.com 联系人: 赵迎春 lcy0508@hotmail.com 电话：05533909558 手机：18155317401 the two genes in the lymphangiogenesis and lymph node metastasis of breast cancer. Methods The expressions of HIF-1α and VEGF-C were investigated by means of immunohistochemistry in samples from 78 cases of breast cancer and 20 cases of breast benign lesions. The density of the lymphatic microvessels immunohistochemically stained by D2-40 antibody was calculated. The relationships between HIF-1α, VEGF-C, LVD and clinicopathological parameters were analyzed statistically. Results HIF-1α expression occurred in 52 out of the 78 tumor samples (66.67%), while VEGF-C expression was observed in 41 out of the 78 tumor samples (52.56%). HIF-1α and VEGF-C expressions in breast cancer were significantly higher than those in beingn disease (15% and 10%; χ²=17.26, P=0.000; χ²=11.71, P=0.001). The expressions of HIF-1α and VEGF-C were significantly correlated with regional lymph nodal involvement (χ²=5.80, P=0.016; χ²=7.26, P=0.007) as well as late TNM classification (χ²=8.51, P=0.004; χ²=6.02, P=0.014), disregarding the patient’s age, tumor diameter, histological grade and pathologic type (P＞0.05). In addition, HIF-1α expression was positively correlated with VEGF-C expression (r=0.254, P=0.025). Higher LVD was found in both high HIF-1α and high VEGF-C expression cases (t=2.19, P=0.017; t=3.25, P=0.001). Conclusion HIF-1α may play a crucial role in the lymphangiogenesis and lymph node metastasis by regulating the expression of VEGF-C in breast cancer. Therefore, HIF-1α may become a particularly promising target for controlling lymph node metastasis in breast cancer.