Mechanisms of HIF-1α and VEGF-C on the lymphangiogenesis in breast carcinoma / 国际肿瘤学杂志

ABSTRACT

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 effects of 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 with breast cancer and 20 cases with 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％ ; x2 =17.26,P =0.000; x2 =11.71,P =0.001).The expressions of HIF-1α and VEGF-C were significantly correlated with regional lymph nodal involvement (x2 =5.80,P =0.016; x2 =7.26,P =0.007) as well as late TNM classification (x2 =8.51,P=0.004; x2 =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.