The Correlation Between Lymph Node Metastasis And Expression Of VEGF-C And Its Receptor In Breast Cancer

Objective:Breast cancer is a kind of malignant tumor which serious affects women's health.The disease incidence of breast cancer has a trend of increasing.In some areas,especially in some big cities,it has leaped to first place in the malignant tumors.Its ten-year survival rate is approximate 40 percent.In the development of breast cancer,lymphatic metastasis is very common.Many patients died of lymphatic metastasis though we have cleared away the metastatic lymph nodes by operation.Many researches testified that lymph node metastasis and the number of metastatic lymph nodes have definite effects on the prognosis of breast cancer.Therefore ,in the process of diagnosis and therapy of breast cancer,how to check and control lymphatic metastasis is very important.Recently,researchers have found that VEGF-C(vascular endothelial growth factor-C)is also one member of the VEGF family.Its receptors are VEGFR-2 and VEGFR-3.Researches have found that VEGFR-2 can bind to VEGF-C or VEGF-A,while VEGFR-3 can bind to VEGF-C,but not to VEGF-A.Thus,the peculiar receptor ofVEGF-C is VEGFR-3(vascular endothelial growth factor receptor-3), also named Flt-4(fms-like tyrosine kinase-4).VEGF-C is a peculiar regulator of lymphatic endothelial cells.It mainly induces chemotaxis of lymphatic endothelial cells,cellular proliferation and hyperplasia of lymphagion.Up till the present moment,there are many researches relating to the correlation between VEGF-A and lymphatic metastasis.But the receptors of VEGF-A are VEGFR-1 and VEGFR-2,which mainly expressed in the vascular endothelial cells.VEGF-A can effectively induce angiogenesis and increase vascular permeation,and it has nothing to do with lymphagenesis. Therefore,many researchers overestimated the role of VEGF-A.In consequent,the role of lymphagenesis in tumor metastasis is generally overshadowed by the greater emphasis placed on the blood vascular system.Now,many researches have testified that lymphatic metastasis of malignant tumors is closely associated with the expression of VEGF-C.But up to now,the researches about the correlation between lymphatic metastasis of breast cancer and VEGF-C are poor.In this study,we examined the expression of VEGF-C and its receptor VEGFR-3 in human breast carcinoma tissue by using immunohistochemical staining ,to check whether there is a correlation between lymph node metastasis and expression of VEGF-C and its receptor in breast cancer.Our objective is to study the molecular mechanism underlyinglymphatic metastasis of breast cancer,and to provide theoretical basis for anti-lymphagenesis and then for anti-lymphatic metastasis of breast cancer.Method:The expression of VEGF-C and its receptor VEGFR-3 were examined by immunohistochemistry in 5 specimens of breast fibroadenomas,3 specimens of normal breast tissue,38 specimens of breast cancer with lymphatic metastasis,and 24 specimens of breast cancer without lymphatic metastasis(all be confirmed by pathologic diagnosis).The staining result was analyzed by using the optical microscope,then investigating the difference between breast cancer with and without lymphatic metastasis.Results:In breast fibroadenomas and normal breast tissue,we haven't found the expression of VEGF-C and VEGFR-3.VEGF-C is expressed mainly in carcinomatous cytoplasm of breast cancer.The positive reaction appears brightly brown-yellow staining.The positive ratio of VEGF-C expression was 68.42%(26/38) in lymph-node-positive group and 33.33%(8/24) in lymph-node-negative group.There is statistical difference between them(p<0.01).On the other hand,the expression of VEGF-C isn't associated with age,the size of tumor and the condition of menses(p＞0.05).The immunostaining of VEGFR-3 was localized in the carcinomatous cytoplasm and membrane,and also in theendothelial of the lymphatic vessels constituting different size of elongated and narrow formation.The lumen was observed usually at the periphery of the tumor.The positive reaction appears brightly brown-yellow staining.The positive rat...