The Relation And Significance Of The Expression Of EGFR And VEGF In Breast Cancer

PrefaceBreast cancer,one of the most common malignant women tumor in recent years, with the incidence showed a rising trend year by year in China,have been ranked the first one of malignant tumors.So,it has became serious harmful to the health of women. The metastasis of breast cancer is one of the main factors affecting survival rate,breast cancer metastasis is associated with a number of factors,such as MVD,EGFR,VEGF, etc.Angiogenesis in tumor generation and metastasis plays an important role,the prior study shows that:EGFR and VEGF is associated with the generation and development.EGFR is one of the members in the 4 epidermal growth factor receptor family members,EGFR,a 1186 amino acid glycoprotein containing,with 170KD molecular weight and tyrosine kinase activity,is a transmembrane cell surface distribution sensor, consisted of 3 components:the extracellular domain,transmembrane and intracellular. Its N-terminal extracellular domain can be divided into four sub-areas site,which is combined with the EGFR ligand(transforming growth factor-a,epidermal growth factor,double-modulin,etc.);transmembrane domain with a component of lipophilic helical polypeptides;intracellular region contains a conserved tyrosine kinase phosphorylation site.EGFR is a monomer in the non-active state,once EGFR and its ligand binded,the homologous or heterologous dimers will be formed,receptor in intracellular region will be phosphorylated and self-start a series of intracellular signaling cascade.Associated with the above signal transmission protein are: phospholipase C-71,phosphatidylinositol 3-kinase,serine threonine protein kinase,ect. Finally the relevant protein will be activated,promoting cells from G phase to S phase. EGFR also play an important role in cell derivatization,the interrelated study has revealed that EGFR offered significance contribution in the cancer development process,such as angiogenesis,metastasis of tumor cells,adhesion and apoptosis.The expression of transforming growth factor-a and EGFR in tumors often indicated further progression and poor prognosis.Earlier study found that ER missing accompanied by high expression of EGFR at the same time in estrogen-independent breast cancer cell lines and clinical tumor antagonizing endocrine therapy,this revaled a dependablity between EGFR and estrogen-independent breast cancer,which can be find in many other breast cancer cell lines.It is very important analyzing the changes of EGFR in the tumorous patients by standardized quantitative methods.Further studying the regulation mechanisms of EGFR in breast cancer tissue is a very crucial research topic for assessment of breast cancer prognosis.Although there are few understand to the molecular basis of EGFR gene expression in breast cancer tissue up to now,they are relevant to many human tumors.VEGF,as a key angiogenesis regulatory factors in involved in a variety of physiological and pathological conditions of vascularization.VEGF family,including VEGF,PLGF,VEGF-B,VEGF-C and VEGF-D,one of the most studied is VEGF. VEGF is constituted by four isomers:VEGF121,VEGF165,VEGF189 and VEGF206, VEGF121 and VEGF165,with strongest biological activity,of which the difference is: VEGF121 is a secreted protein lacking exon 7-encoded amino acids residues and can not be combined with heparin.VEGF widely distributed in the body,and showed variety biological functions by interactions with its two main receptor(VEGFR-1, VEGFR-2).For the high expression of VEGF receptors in vascular endothelial cell, the known biological effects of VEGF is mainly concentrated on endothelial cells: promotion endothelial cells survival,proliferation,migration,formation of tubular structures,promotion vascular permeability and vasodilation.A large number of studies have shown that the growth and metastasis of tumor depend on angiogenesis induced by VEGF;on the other hand,high expression of VEGF in ischemic region can induce to generate new blood vessels to restore region blood supply.We investigated the expression of EGFR,VEGF in breast cancer tissue by immunohistochemical methods, to explore the relationship between its expression and lymph node metastasis.Materials and MethodsStudyCollection 74 breast surgeon cases from January 2007 to December 2007 in The First Affiliated Hospital of China Medical University.Paraffin-embedded specimens were confirmed by pathology,all cases are Female,without preoperative radiotherapy and chemotherapy,Age from 31 to 76 years old,with average age 52.2 years old.Of which,50 cases with breast infiltrating ductal carcinoma,the other 24 cases with ductal carcinoma accompanied early invasion.Randomly selected 30 cases with breast fibroadenoma in the same period as the control group.Methods:SP immunohistochemical method.Observation of two double-blind biopsy, counting the number of positive cells in 100 tumor cells in the randomly selected five high power field by immunohistochemical method.Positive results with known gastric biopsy for positive control,using PBS to replace primary antibody solution for negative control.SPSS 16.0 data analysis software applications,application x~2 test,P＜0.05 for statistical significance.The experimental results 74 cases of breast cancer, EGFR-positive 48 cases(64.9%),VEGF-positive 50 cases(67.6%).EGFR-positive three cases(10%) in breast fibroadenoma,and VEGF-positive 4 cases(13.3%),P＜0.05. The positive expression rate in the two groups has a statistically significant difference in the TNM staging,histological type and lymph node metastasis of breast cancer patients(P＜0.05).In different age and tumor size of breast cancer patients,there was no statistical significance(P＞0.05).ConclusionCombined detection of EGFR and VEGF is important for assessment of lymph node metastasis of breast cancer.