Expression Of Vascular Endothelial Growth Factor(VEGF), Vascular Endothelial Growth Factor C(VEGF-C), Fms-like Tyrosine Kinase 4(Flt-4), Microvascular Desity(MVD) And Lymphatic-vessel Density (LVD) In Breast Cancer And Its Clinical Significance

Objective: Breast cancer is one of the malignant tumorswhich is commonly found in females. Metastasis andrecurrence of breast cancer are important reasons which affectthe quality of life and the survival time of patients. Recentstudies have found that there is close relationship between thegeneration of blood vessel and lymph vessel of breast cancerand its progress, invasion and prognosis. Now, the research onthe generation of blood vessel and lymph vessel of tumor isfocused on the vascular endothelial growth factor family.Vascular endothelial growth factor (VEGF) is believed to beone of the most important factors to stimulate the proliferationof vascular endothelial cells. In recent years, people pay moreattention to its important role in angiogenesis and metastasis oftumor. Vascular endothelial growth factor C (VEGF-C) is a newmember of VEGF family, studies have shown that it is aspecific regulating factor for lymphatic endothelial cells.VEGF-C can combine with its receptor Flt-4(fms-like tyrosinekinase 4 ) and accelerate the process of lymph vesselhyperplasia and lymph nodes metastases. In this study, wedetected the protein expression of VEGF, VEGF-C, Flt-4 inbreast cancer, analyzed the relationship between them andMVD, LVD, Flt-4 positive vessel number, in order to clarifythe relationship between angiogenesis and lymphangiogenesisand their mechanism in metastasis of breast cancer.Methods: The expressions of VEGF, VEGF-C, Flt-4,MVD, LVD and Flt-4 positive vessel number were studied in105 patients with primary breast cancer by S-Pimmunohistochemical technique. χ2 test and Logisticregressions were used to analyze the data.Results: 1. Relationship of VEGF, VEGF-C, Flt-4, MVD,LVD and Flt-4 positive vessel number: In 105 patients, therewere 65 patients with positive VEGF expression (61.90%), 43patients with high MVD expression (40.95%), significantcorrelation was found between VEGF and MVD (P<0.001).There were 46 patients with positive VEGF-C expression(43.81%), 82 patients with positive Flt-4 expression (78.10%),44 patients with high LVD expression (41.90%), 43 patientswith high Flt-4 positive vessel number expression (40.95%).VEGF-C was significantly related to Flt-4 (P<0.01), moreover,they all had significant correlation with LVD or Flt-4 positivevessel number (P<0.01,respectively), but they were notsignificantly related to MVD(P>0.05).2. Relationship between breast cancer clinicopathologicalcharacteristics and the expressions of VEGF, VEGF-C, Flt-4,MVD, LVD or Flt-4 positive vessel number: There was nocorrelation between VEGF,MVD or Flt-4 positive vesselnumber and tumor size, age or lymph node status(P>0.05,respectively). The expressions of VEGF-C,Flt-4 orLVD had no correlation with tumor size (P>0.05,respectively),but the expressions of them were significantly higher in lymphnode metastasis group than that of no lymph node metastasis(P<0.05,respectively). Flt-4 was significantly related to age(P<0.01).3. In the patients who had blood metastasis, theexpressions of VEGF and MVD in axillary-node-negativegroup were significantly higher than that ofaxillary-node-positive group (P<0.05,respectively), but theexpressions of VEGF-C, Flt-4 and LVD were significantlylower than that of the latter(P<0.05, respectively). But for Flt-4,no significant difference was found between two groups.(P>0.05).4. Relationship between blood metastasis and expressionsof VEGF, VEGF-C, Flt-4, MVD, LVD, Flt-4 positive vesselnumber or clinicopathological characteristics: The expressionsof MVD and VEGF-C in breast cancer were closely related toblood metastasis(P<0.01,respectively); no correlation wasfound between VEGF,Flt-4,Flt-4 positive vessel number,age or tumor size and blood metastasis.Conclusions: 1.VEGF promotes angiogenesis; VEGF-C is...