The Expression Of COX-2,VEGF And CD105 In Breast Cancer And Clinical Significance

Tumor metastasis is the characteristic biological feature of malignant tumor, and the leading cause of malignant-tumor-related death. neovascularization is the precondition of tumor growth and tumor metastasis. The newly formed blood vessels not only provide nutritional support but also are the main pathway for the circulatory system. Until now,the mechanism of metastasis through blood in breast cancer is still not clear. Further research in mechanism of metastasis through blood will possiblely extend patients' lifespan and decrease patients' mortality rate by effectively inhibiting the tumor vascularization., which supports new pathway for the treatment of breast cancer.Recent studies demonstrate that there is a close relationship between Cyclooxygenase-2 (COX-2) and blood vessel formation. Its high expression may promote tumor cells to release vasogenic material and has a important role in the regulation of neovascularization. But the mechanism is unclear. Vascular endothelial growth factor (VEGF) is the strongest known to promote tumor angiogenesis factor, which can specifically act on the endothelial cells of blood vessel and in vivo induce blood vessel formation. Vascular endothelial growth factor (VEGF) is the strongest known to promote tumor angiogenesis factor, which can specifically act on the endothelial cells of blood vessel and in vivo induce blood vessel formation. but the relationship between the expression of COX-2 and VEGF in breast cancer tissue and tumor microcapillaries desity is hardly reported.This study used the S-P method of immunohistochemistry to examine COX-2, VEGF, and CD105 expression in breast cancer, the relationship between its expression and the biological character of breast cancer ,and the relationship between its expression and patients' survival were analyzed to determine its significance on prognosis.Materials and Methods1. Patientsspecimen of 117 primary breast cancer patients undergoing modified radical mastectomy and conservative treatment was collected and the histomicroarray was formed using randomized allocation .the range of patient's age is 29～74 years, with the average 51.4 years. All the patients didn't recieive chemotherapy before surgery and received chemotherapy after chemotherapy in our department .the follow-up data was complete with the average follow-up duration 42.3 months ranging from 4 months to 70 months.2. AgentRabbit-anti-human COX-2 monoclonal antibody, Mouse-anti-human VEGF monoclonal antibody, Mouse-anti-human CD105 monoclonal antibody, SP examination kit, DAB colored solution were purchased from Fuzhou Mai xin bio-tech Developm- eent Company. The second antubodies was purchased from Beijing Zhongshan Goldenbrige Biotechnology.3. MethodsThe behavior leaMethods: the S-P method was used to determine the immumohistochemical results, the laboratory procedure were operated strictly according to the manufacture's instruction and the primary antibody was replaced by PBS as negave control, with positive sides of Rectal Cancer COX-2 and VEGF as control group.4. AssessmentThe MVD count marked by CD105 shows brown single epitheilum or the endothelial cell group, neighboring. As long as they are separated form the neighboring capillaries ,tumor cells and other connective tissues,they are reguarded as microcapillaries. the number of the microcapillaries is counted 200×magnified light microscope. take the mean value for the MVD. when there are brown yellowish particles in cytoplasm and nuclear membrane,the COX-2,VEGF is determined as positive,which is divided nito hypoexpression ,moderate expression and hyperexpres-sion according to cross product of positive cell percentage and the coloring intensity. The positive rate was expressioned by"moderate degree expression+ high degree expression" or negative rate "low-level expression". 5. Statistical analysisThe average value is compared using T test, survival rate is calculated using Kaplan-Meier method, survival time is compared using Log-Rank test, take P<0.05 as having statisital significance for comparing the rate of two samples by x~2 test.All the statistical analyses is performed by using SPSS11.5 statistics software package.Results1. The expression of COX-2 VEGF in breast cancer tissue and clinical pathology: COX-2 positive expression rate was 55.6%, COX-2 positive expression in different clinical stages (P=0.01,r=0.238), lymph node metastasis (P=0.01,r=0.238), HER-2,ER status (P=0.025,r=0.218), is statistically different , but isn't related to age, tumor size and pathological type(P>0.05). The VEGF positive expression is 66.7%, which is related to lymph node metastasis, clinical stage(P<0.05).2. MVD expression and COX-2, VEGF taking CD105 as a marker of neovscularizati- on ,breast cancer MVD value Isn't related to tumor size and hormone receptor status ,but is positively related to lymph node metastasis and clinical stage (P=0.029, r=0.201). (P=0.023, r=0.210).3. Breast cancer relapse and COX-2 and VEGF expression: After reviewing surgery specimen of the breast cancer patients having relapse, COX-2, VEGF positive expression rate is (79.31%, 86.21%) is higher than nonrelapse patients (47.73%%, 60.23%).(P=0.003,P=0.01).4. COX-2,VEGF expression and postoperative survival relationship (Kaplan-Meier): The Kaplan-Meier survival curve analysis Log-Rank test shows COX-2, VEGF expression and disease free survival rate were negatively correlated(P=0.004,P=0.032) . It can be found that common positive suivival period acquired by common test is shortest (P=0.005) .5. Multivariate analysis showed that ER, PR, HER-2 positive expression and tumor size, lymph node metastasis and COX-2 expression was an independent prognostic factors in breast cancer.Conclusion1. The hyperexpression of COX-2 and VEGF in breast cancer is positive correlation, the expression of COX-2 leads to breast cancer invasion and metastasis possibly by promoting VEGF expression.2. COX-2 and VEGF negative expression patients surpass positive patients in the prognosis, and common positive patients were worst prognosis. Both are indicators of poor prognosis.3. CD105 expression in breast cancer is indicator of tumor new vessels , which marked capillary density is a possible value.