VEGF-C及其受体Flt-4在乳腺癌细胞增殖及转移中的作用

背景与目的:血管内皮细胞生长因子-C(vascularendothelialgrowthfactor-C,VEGF-C)是VEGF家族成员之一,是惟一可与淋巴管内皮细胞表面受体VEGFR-3(即fms-liketyrosinekinase-4,Flt-4)结合并调节淋巴管生理功能的因子。目前发现VEGF-C/Flt-4系统在多种肿瘤的转移中起调控作用,但对该系统在乳腺癌方面的研究国内外报道很少。本实验旨在探讨VEGF-C/Flt-4在乳腺癌增殖及转移中的作用和意义。方法:采用免疫组织化学方法对101例乳腺癌组织切片染色,观察乳腺癌组织中VEGF-C、Flt-4、增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)的表达情况。结果:101例乳腺癌组织中,VEGF-C阳性率为93.1%(94/101),Flt-4阳性率为86.1%(87/101),且Flt-4阳性指数随VEGF-C表达的增强而增加(r=0.816,P<0.001);PCNA的阳性率为88.8%(89/101),且随着VEGF-C表达强度增强,肿瘤细胞增殖活性也随之增强(r=0.673,P<0.001)。VEGF-C阳性指数在转移组(61.89±17.79)明显高于未转移组(44.28±17.87)(P<0.05)。随着癌细胞VEGF-C表达强度增强,Flt-4阳性脉管数也随之增加,各组间均有显著性差异(P<0.001)。乳腺癌中Flt-4阳性脉管数在淋巴结转移组(15.55±3.63)明显高于未转移组(10.71±2.90)(P<0.05)。结论:VEGF-C及其受体Flt-4在人乳腺癌细

Roles of VEGF-C and its receptor Flt-4 in proliferation and metastasis of primary breast cancer

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor-C(VEGF-C) is a member of VEGF family and the only factor that can combine receptor VEGFR-3 (fms-like tyrosine kinase, Flt-4) located at endothelium of lymphatic vessel and modulates the physiological function of lymphatic vessel. Previous study showed that VEGF-C/Flt-4 system play a modulating role in metastasis of many kinds of tumors, but there were few reports about its function for primary breast cancer at home and abroad. The objective of this study was to identify the function of VEGF-C/Flt-4 system in proliferation and metastasis of primary breast cancer and its significance. METHODS: A series of 101 primary breast cancer specimens were detected for the expression of VEGF-C, Flt-4,and PCNA by Immunohistochemical methods. RESULTS: Among 101 cases of breast cancer, the positive rate of VEGF-C was 93.1% (94/101), the positive rate of flt-4 was 86.1% (87/101). With the increase of the expression of VEGF-C, the positive index of flt-4 increased (r=0.816,P< 0.001). The positive rate of PCNA was 88.8% (89/101). With the increase of the expression of VEGF-C, the proliferation activity of PCNA was stronger (r=0.673,P< 0.001). The positive index of VEGF-C in lymph node metastases group (61.89+/-17.79) was significantly higher than that of no lymph node metastasis group (44.28+/-17.87)(P< 0.05). With the increase of VEGF-C protein level, the number of flt-4 positive vessels increased and significant differences among these groups were observed (P< 0.001). The number of flt-4 positive vessels in lymph node metastases group (15.55+/-3.63)was significantly higher than that of no lymph node metastasis group (10.71+/-2.90 ) (P< 0.05). CONCLUSION: VEGF-C and Flt-4 are overexpressed in primary breast cancer and related to lymph node metastasis. VEGF-C can promote proliferation of breast cancer cell. VEGF-C/flt-4 system can promote vasculogenesis in stroma of breast cancer. The number of Flt-4 positive vessels is closely related to lymph node metastasis.