The Expression And Significance Of Angiopoietin-2,Tie-2,CD34 In Breast Carcinoma

Background and Objective: Breast carcinoma is a malignant disease which seriously threats female health. The incidence of breast carcinoma accounts for the first position of female malignant tumors. Though the history of the treatement research of berast carcinoma has more than 100 years, especially in recent twenty years, the diagnosis and treatment technology of breast carcinoma have made great progress, but about 400 thousand women are dying of it all over the world each year. At present, the research of the carcinogenesis and malignant progression of breast carcinoma still is one of the hotspots of breast carcinoma research. Researching deeply the mechanism of the carcinogenesis and development of breast carcinoma have important significance for the choice and implement of the treatment and prevention measures of breast carcinoma.In recent years, the studies about the function of angiogenesis(Ang) ,its receptor and CD34 have gradually increased and validated, their important significance in the carcinogenesis and development of the tumors have been confirmed .Angiopoietin is a type of angiogenesis-related proteins witch formed byAng-1,Ang-2,Ang-3 and Ang-4.Angl and Ang-2 are related to angiogenesis.Ang-2 is secreting type glycoprotein, witch molecular weight is 75kD.Ang-2 is mainly in the form of homodimers.Ang-2 play a role through integrating with Tie-2 witch is a endothelial cell-specific tyrosinase receptor.When Ang-2 combined with Tie-2 in endothelial cells, Ang-2 can weaken interaction between endothelial cells and endothelial cells, endothelial cells and supporting cells. It can also destroy the stability of vascular structures, resulting the sprouting of capillary and the formation of new vessels. Ang-2 is an early marker induced angiogenesis of tumor witch is related to the number of tumor vessels, the clinical staging and prognosis.CD34 is a high-glycosylation transmembrane protein witch molecular weight is 105～120 kD . CD34 expresses in vascular endothelial of normal and tumor small blood vessels .It is a new antigen associated with the new small blood vessels.The mechanism is not yet clear that its role in vascular endothelial. However, its expression in endothelial neovascularization is much more than non-endothelial neovascularization , and suggesting its possible role of angiogenesis. Its expression in vascular endothelial cells make it into the most sensitive vascular endothelial marker.At present, the documents reporting the relations of Ang-2 expression and the clinical pathology features of breast carcinoma are less.The research in the correlation of the expression of Ang-2 and Tie-2 in breast carcinoma tissue was not reported in documents in our country. In this experiment, we investigated the expression conditions of Ang-2, Tie-2 and CD34 in breast ductal carcinoma tissue and control normal breast tissue, fibroadenoma breast tissue with immunohistochemisty, and analyzed the respectively expression difference of Ang-2, Tie-2 among different breast tissues and between breast ductal carcinoma in situ and breast invasive ductal carcinoma tissues, the associations between the expressions of Ang-2, Tie-2 and the clinical pathology features of breast invasive ductal carcinoma tissues and the correlation between Ang-2 expression and Tie-2 expression in breast ductal carcinoma tissues.Discussing the roles of Ang-2 and Tie-2 in the carcinogenesis and development of breast carcinoma and the likely molecule mechanism to supply a experiment basis for introducing Ang-2, Tie-2 as new mark molecules into the clinical theatment of the tumors.Methods: Immunohistochemistry streptavidin-peroxidase method was used to examine the expression of Ang-2, Tie-2 ,CD34 protein in 16 cases of normal breast tissue,13 cases of breast fibroadenoma tissue, 10 cases of breast ductal carcinoma in situ and 42 cases of breast invasive ductal carcinoma tissue. Furthermore, the respectively expression differences of Ang-2, CD34,Tie-2 among different breast groups and between breast ductal carcinoma in situ and breast invasive ductal carcinoma tissues, the associations between their expressions with the features of clinical pathology of invasive ductal breast carcinoma were also analyzed with non parameter test ,x~2 test. The expression correlation between Ang-2 and Tie-2 in breast ductal carcinoma was analyzed with spearman correlation test.Results: 1. Ang-2, Tie-2 and CD34 lightly expressed in all normal breast and fibroadenoma breast control tissues; the expressions of Ang-2, Tie-2 and CD34 were distinctly increased in breast ductal carcinoma tissues . The respectively expression differences of Ang-2, Tie-2 and CD34 were significant among three groups (P<0.05). Further, abnormal expression distribution of Ang-2 could be seen in breast carcinoma stroma; abnormal expression distribution of Tie-2 could be seen in breast ductal carcinoma cell cytoplasma.2. The positive expression rates of Ang-2,Tie-2 in breast invasive ductal carcinoma (83.33%, 83.33% respectively ) were higher than those of breast ductal carcinoma in situ (50.00%, 40.00% respectively ).The expression of Ang-2 had significant difference between two groups (P=0.039).The expression of Tie-2 had significant difference between two groups (P=0.010).3.The MVD marked by CD34 in breast invasive ductal carcinoma (186.47±26.47) was higher than that breast ductal carcinoma in situ (163.44+24.84) . The expression of CD34 had significant difference between two groups (P=0.021).4. The positive expression rate of Ang-2 in breast invasive ductal carcinoma of stage III (89.47%, 17/19) was higher than that in breast invasive ductal carcinoma of stage I - II (56.52%, 13/23),there was significant difference between them(P=0.020). The positive expression rate of Ang-2 in breast invasive ductal carcinoma group with lymph node metastasis (84.38%, 27/32) was higher than that in breast invasive ductal carcinoma group without lymph node metastasis (50.00%, 5/10). There was significant difference between them (P=0.004). The positive expression rate of Ang-2 in breast invasive ductal carcinoma group≥3cm in tumor diameter (89.66%, 26/29) was higher than that in the group < 3cm in tumor diameter (53.85%, 7/13). There was significant difference between them (P=0.016).5. The positive expression rate of Tie-2 in breast invasive ductal carcinoma of clinical stage III (89.47%, 17/19) was higher than that in breast invasive ductal carcinoma of stage I -11(52.17%, 12/23), there was significant difference between them(P=0.010). The positive expression rate of Tie-2 in breast invasive ductal carcinoma group with lymph node metastasis (78.13%, 25/32) was higher than that in breast invasive ductal carcinoma group without lymph node metastasis (40.00%, 4/10). There was significant difference between them (P=0.032). The positive expression rate of Tie-2 in breast invasive ductal carcinoma group≥3cm in tumor diameter (82.76%, 24/29) was higher than that in the group < 3cm in tumor diameter (38.46%, 5/13). There was significant difference between them (P=0.007).6. The expression of Ang-2 and Tie-2 in breast ductal carcinoma was increased .There was significant correlation between them (rs=0.672, P=70.000) .Conclusions: 1. The expression of Ang-2 increasted in breast ductal carcinoma ; The increasted expression of Ang-2 significantly correlated with the invasion , lymph node metastasis of breast ductal carcinoma and the tumorous size of breast invasive ductal carcinoma . It indicates the increasted expression of Ang-2 takes part in the carcinogenesis and progression of breast ductal carcinoma in a certain degree .2. The expression of Tie-2 increasted in breast ductal carcinoma; The increasted expression of Tie-2 significantly correlate with the invasion, lymph node metastasis of breast ductal carcinoma and the tumorous size of breast invasive ductal carcinoma. It indicates the increasted expression of Tie-2 closely correlates with the carcinogenesis and progression of breast ductal carcinoma.3. Significant correlation exists between the expression of Ang-2 and that of Tie-2 in breast ductal carcinoma. They may take part in the carcinogenesis and progression of breast ductal carcinoma together in complementary or cooperative manner.4. Ang-2 and Tie-2 are the important mark to evaluate the clinical pathology features of breast invasive ductal carcinoma. Investigating both expression conditions may help to understand and evaluate the malignant condition of breast carcinoma and the prognosis of the patients in multiple respects.5 .The expression of CD34 increasted in breast ductal carcinoma.