The Role Of VEGF-C,D/Flt-4 In The Process Of Lymphatic Metastasis In The Early-stage Of Invasive Cervical Carcinoma

【Objective】To investigate the role of VEGF-C,D/Flt-4 in the process of lymphatic metastasis in the early-stage of invasive cervical carcinoma,we assessed the expression of VEGF-C,VEGF-D,and their receptor Flt-4,we also assessed lymphatic vessels density(LVD) and Flt-4-positive vessel density(FVD),respectively, by immunohistochemical staining with LYVE-1 and Flt-4.【Methods】VEGF-C,VEGF-D,and Flt-4 were analyzed in 41 cases of early-stage ofinvasive cervical carcinoma employing both immunohistochemistry and RT-PCR method.Simultaneously,Lymphatic vessels density(LVD) and Flt-4-positive vessel density(FVD)were respectively assessed after staining with LYVE-1-specific antibodies and Flt-4-specific antibodies.All of them were correlated with tumor clinicopathologic features.【Results】1.The expression of VEGF-C,VEGF-D,and Flt-4 and its relationship with clinicopathological factors in the early-stage of invasive cervical carcinoma(1) The expression of VEGF-C,VEGF-D,and Flt-4 in the early-stage of invasive cervical carcinoma.The positive rate expression of VEGF-C,VEGF-D,and Flt-4 protein were 48.7%,58.5%,and 63.4%,respectively;and the positive rate expression of VEGF-C,VEGF-D,and Flt-4 mRNA were 51.2%(21/41),63.4%(26/41),63.4%(26/41),which were correlated with the protein level correspondingly.(2) The relationship between VEGF-C,VEGF-D,and Flt-4 and clinicopathological factors in the early-stage of invasive cervical carcinoma.The expression of VEGF-C,VEGF-D protein were correlated with lymph nodal metastasis, lymphatic vessel invasion,FIGO stage,and histological grade(P＜0.01,P＜0.01, P＜0.05,P＜0.05),but not with menopause or histological classification(P＞0.05, P＞0.05).The expression of Flt-4 protein was correlated with lymph nodal metastasis, lymphatic vessel invasion,and FIGO stage(P＜0.05,P＜0.05,P＜0.01),but not with menopause,histological grade,and histological classification(P＞0.05,P＞0.05, P＞0.05).2.The relationship between LVD,FVD and clinicopathological factors in the early-stage of invasive cervical carcinoma The LVD was correlated with FIGO stage,histological grade,lymph nodal metastasis,and lymphatic vessel invasion(P＜0.05,P＜0.01,P＜0.01,P＜0.01,P＜0.01),but not with menopause or histological classification(P＞0.05,P＞0.05).The FVD was correlated with FIGO stage (P＜0.01),but not with menopause,histological grade,lymph nodal metastasis, lymphatic vessel invasion,and histological classification(P＞0.05,P＞0.05,P＞0.05, P＞0.05 P＞0.05).3.The relationship between VEGF-C,VEGF-D,and Flt-4 and LVD,FVD in the early-stage of invasive cervical carcinoma.The expression of VEGF-C and VEGF-D protein(P＜0.01,P＜0.01),but not Flt-4 protein(P＞0.05, P＞0.05),were Correlated with both LVD and FVD.【Conclusions】1.The paracrine function of VEGF-C,D/Flt-4 in the process of lymphatic metastasis The lymphanglogenic factors VEGF-C and VEGF-D,which are secreted by cervical carcinoma cells,could induce tumor lymphangiogenesis,provide extra lymphatic channels,thus promoting the spread of tumour cells,by activating the tyrosine kinase receptors Flt-4 in lymphatic endothelial cells through a autocrine-signaling mechanism.2.The autocrine function of VEGF-C,D/ Flt-4 in the process of lymphatic metastasis As the receptor of VEGF-C and VEGF-D,Flt-4,which are mainly expressed by endothelial cells,are also expressed by cervical carcinoma cells,VEGF-C,D/Flt-4 may play an important role in the process of lymphatic metastasis in the early-stage of invasive cervical...