Relationship Between The Expression Of TP, VEGF-D, VEGFR-3 And Lymphangiogenesis Of Breast Carcinoma

The breast cancer is the most frequent tumor in female breast and occupies 7%-10% in all malignant tumors,second only uterine cervix cancer, it threatens female health and life seriously. Lymph node metastasis is a more easely way to breast cancer ,lymphangiogenesis can promote the metastasis of breast cancer. Lymphangiogenesis is a focal point of cancer research these years.Lymphangiogenesis isthat tumor promoting is a important way for lymph node metastasis , Lymphangiogenesis of tumor can cause the increase of lymphatic vessel density,to promote the tumor cell entering lymphatic vesseland metastasis. Thymidine phosphorylase (TP) is a homodimer which consists of about 389 amino acid residue and the molecular mass is about 48.3-49.0×10~3 ,locating at cellular nueleus or cytolymph. TP can't direct to stimulate the desintegration and proliferation of EC,but it has chemotaxis and stimulates the immigrate of EC,possesses the enzymatic activity. TP effect thymine deoxyriboside specificly. Let produces reversible phosphorylation, its production 2-dDR can introduce the angzogenesis .In breast carcinoma tissue, the expression of TP is higher obviously than the normal tissue nearly. It can promote the vegetation of tumorous and the angiogenesis through enhancing the immigrating of endothelial cell, opposing the corpuscular apoptosis ,introducing the oxidative stress promoting the releasing of angiogenesis factor .TP plays critical role in tumor and Lymphangiogenesis.Vascular endothelial growth factor-D(VEGF-D) is an important factor of regulating the nascent of lympgatic vessels in tumor's interstitial substance. It locates at the endochylema of EC and the cellula intersitialis of tumor tissues. When it binds FLt-4(vascular endothelial growth factor receptor-3,VEGFR-3 or named FLt-4),the RAFTK monophenolase phosphorylates, activates the cytoskeletal protein Paxillin,promoting the immigration of endotheliocyte in lympgatic vessel, meanwhile ,it can stimulate the activation of the signal transolution pathway of Ras/MAPK or JAK,induce the actin's recombination of endothelial cell in lympgatic vessel, stimulate its proliferation. Its receptor VEGFR-3 resists in all endothelial cell at the primary stage in embryogenesis, locates subsequently in vein and lympgatic vessel.It's a specific tumor marker of endodermis in mature lympgatic vessel. During the production of lympgatic vessel,tumor cell and the endothelial cell interact. The tumor cell can secrete some factors to promote the activation of endothelial in lympgatic vessel and the tumor cell entering lympgatic vessel. In human tumor tissue ,there can be seen the lympgatic vessel which is neogenesis or dilation or having the embolus of cancer near the tumor.There are overexpression of VEGFR-3 in the endothelial cell of lympgatic vessel when the lymphoid node develops carcinomatous metastasis.The VEGFR-3 starts to express again in tumor new vascular endothelial cell ,it cues that the regulation system of VEGF-D/VEGFR-3 can regulate the production of tumor mterstitium vasoganglion and lymphatic vessel.But lymphatic vessel is the chief pathway of diffusion.The production of lympgatic vessel possesses an important significance in the spread of tumor and the predict of preservataion.This project use immunohistochemistry (SP assay)to observe the expression of TP, VEGF-D, VEGFR-3 and lympthatic vessel density (LVD) in breast carcinoma tissue 37 cases and normal mammary gland tissue 30 cases. We carry out the experiment to explore the expression of thymidine phosphorylase (TP),vascular endothelial growth factor(VEGF-D),VEGF receptor-3(VEGFR-3)and Lymphangiogenesis to explore the markers of lymphatic endothelium,the relation to clinical biogical behaviourand prognosis. Methods:1. Immunohistochemistry (SP assay) was used for detecting the expression of TP,VEGF-D and VEGFR-3 and lympthatic vessel density (LVD) in breast carcinoma tissue 37 cases and normal mammary gland tissue 30 cases.2. Statistical treatment: software SPSS 10.0 was used to data statistical analysis . Chi-square test was used to compare positive rate and correlation analysis was employed to analysis two sample.P values less than 0.05 are considered significant.Results:1. The masculine expression rate of TP protein is 46.67% in normal lacteal gland tissue; The masculine expression rate of TP protein is75.67% in breast cancer tissue.The contrast have statistical significance between both. (p<0.05) . In breast cancer tissue., the masculine expression rate of TP protein have not significant deviation in age and the magnitude of tumor. The masculine expression rate of TP protein have significant deviation in lymphoid node extension and the grading of histology (p<0.01,p<0.05) .The counts of lymph vessel were significantly highter in the positive cases of TP (16.52±3.81)/HPthan that in negative ones of TP (9.12±3.43) /HP in breast cancer (p<0.01)2. The masculine expression rate of VEGF-D is 13.33% in normal lacteal gland tissue; The masculine expression rate of VEGF-D is 78.38% in breast cancer tissue. There are significant deviation between both. (p<0.01) . In breast cancer tissue., the masculine expression rate of VEGF-D is independent in age(p>0.05), But they have significant deviation in the magnitude of tumor, lymph node metastasis and the grading of histology (p<0.01,p<0.05,p<0.05) .The counts of lymph vessel were significantly highter in the positive cases of VEGF-D than that in negative ones of TP in breast cancer (p<0.01)3. The masculine expression rate of VEGFR-3 is 10.00% in normal lacteal gland tissue; The masculine expression rate of VEGFR-3 is 56.75% in breast cancer tissue.. There are significant deviation between both (p<0.01) . In breast cancer tissue., the masculine expression rate of VEGFR-3 have not obviously age difference (p>0.05) ,But they have significant deviation in the magnitude of tumor, lymphoid node extension and the grading of histology (p<0.05,p<0.01,p<0.05) . The counts of lymph vessel were significantly highter in the positive cases of VEGFR-3 than that in negative ones of TP in breast cancer (p<0.01)4. The counts of lymph vessel were significantly highter in breast cancer( 14.68±14.82)/HP than that in normal mammary gland tissue (4.62±4.95)/HP , p<0.01;LVD value in lymph node metastasis grou (13.62±12.41)/HP was higher than that in non lymph node metastasis group (7.61±3.22/HP,p<0.01 ,that in I staging(7.82±3.21)/HPwas lower than that of II staging(9.65±2.22)/HP, p<0.01, II staging was lower that of IIIstaging(16.28±3.6)/HP, p<0.01.5. Dependability of TP,VEGF-D,VEGFR-3 expression in breast cancer tissue: the consequence manifest in statistics analysis, TP and VEGF-D, TP and VEGFR-3,VEGF-D and VEGFR-3 have correlated relation(p>0.05,p>0.05,p>0.05).Conclusions:1. The positive rate of the expression of TP, VEGF-D,VEGFR-3 protein in thetissues of breast carcinoma were higher than that in the tissues of normal breast, which are significant difference . The expression of TP, VEGF-D,VEGFR-3 protein is not significant difference with age, size of tumor, lymph node metastasis, grade in the tissues of breast carcinoma. The counts of lymph vessel were significantly highter in the positive cases of TP than that in negative ones of TP in breast cancer. It indicates that TP, VEGF-D,VEGFR-3 might promote lymphoagiogenesis in breast cancre tissues.2. The counts of lymph vessel were significantly highter in breast cancer than that in normal mammary gland tissue , LVD value in lymph node metastasis group was higher than that in non lymph node metastasis group, that is significant different with grade in the tissres of breast carcinoma. LVD should be related to lymphagiogenesis and lymph nodemetastasis.3. The positive correlation of the expression of TP, VEGF-D , VEGFR-3 was analyzed by statistics, and the results showed relative and they played synergistic effect during the process of occurrence and development of breast carcinoma.The increased expression of TP and VEGF-D and VEGFR-3 shoud be related to lymphangiogenesis and lymphnode metastasis .