Expression Of CCR5 In Breast Cancer And Its Relation With Node Metastasis Of Cancer Cells

【Objective】Breast cancer is the one of the most common malignancy of women,it occurred at an average annual incidence rate of 30.30/100 thousands in the worldwide.Each year1.2 Million women of breast cancer occurred,of which 500,000 died,so breast cancer has become a global concern in the health.Metastasis of breast cancer is the leading cause of death in breast cancer patients,the most common metastatic sites are the axillary lymph nodes,lungs,liver and bones,but skin and kidney metastasis are rare.With regard to the occurrence and specificity of breast cancer molecular mechanisms of transfer,a large number of studies has started.In recent years,the study of relationship between the chemokine,its receptor and breast cancer has catched of for the wide concern,and became a hot spot in this field.Particularly the study of which the interaction between CXCR4,CCR7 and the corresponding ligands, which then how to affect other biological protein factor,and how to control the growth of breast cancer,development and transfer,has been conducted in-depth. This also provides abundant information and basis for the targeting therapy for breast cancer.However,there were less reports about the relationship between CCR5 and breast cancer.Experiments show that content of RANTES is high in breast cancer patients' blood serum.As ligand of CCR5,RANTES may attract tumor cells expressing CCR5 to blood circulation.Accordingly,it makes tumor cells further migrate to target organ.Because of complexity of chemokine receptors and tumor growth,the role of CCR5 in the development of breast cancer need to be further explored.We have detected the expression of CCR5,p53,Ki-67,C-erbB-2,ER,PR in breast cancer,and analyzed above-mentioned prognostic indicators and clinical data,especially about the relationship between CCR5 and axillary node metastasis, and then evaluate these biological markers,especially about the effect of CCR5 in the judgement of the prognosis in breast cancer.【Material and Methods】72 samples were collected from Liaocheng Peoples' hospital from October 1, 2006 to July 31,2007,pathology results of which were breast invasive ductal carcinoma.CCR5 protein were detected by immunohistochemistry in 50 specimens of breast cancer and its corresponding axillary lymph node metastasis,50 ones of fibroadenoma of breast and 40 normal lacteal gland.P53,Ki-67,C-erbB-2,ER,PR were detected by immunohistochemistry in 72 samples,and were statistically analyzed with clinical pathology data.【Results】1.The expression of CCR5 in breast tumorIn order to analyze the relationship between breast tumors and CCR5,we have used immunocytochemistry method to detect 40 cases of normal breast,50 cases of breast fibroadenoma,72 cases of invasive ductal carcinoma(IDC) and the 50 cases of axillary lymph node metastasis of ibreast cancer.The results showed that normal breast tissue did not express CCR5,breast fibroadenoma tissue has the low-positive expression of CCR5 protein(14%,7/50),but The positive expression rate of CCR5 in breast cancer was as high as 84.72%(61/72),CCR5 expression and tips of breast cancer.These indicated that CCR5 may be related to the occurrence of breast cancer.2.The relationship between the expression of CCR5 in breast cancer and clinical pathological parametersIn order to study the significance of expression of CCR5 in breast cancer,we analyzed the relationship between CCR5 expression rate and clinical pathological characteristics,found that there was no relationship between CCR5 and the patient's age,menopausal or not,tumor diameter,or tumor staging,but CCR5 has a positive correlation with lymph node metastasis(x~2=4.982,P=0.026),which indicated CCR5 may prompt breast cancer metastasis.3.The expression of CCR5 in primary breast cancer and metastatic lymph nodesIn 72 cases of breast cancer and axillary lymph node tissue samples,there were 61 cases of primary tumors stained positive(84.72%),accompanied by of which 46 cases with lymph node metastasis,15 cases with no lymph node metastasis,the metastasis rate is 75.41%;in 11 cases of primary tumors stained negative,4 cases with axillary lymph node metastasis,the metastasis rate is 36.36%.In 50 cases with axillary lymph node metastasis,there were 39 ones with positive expression of CCR5 in primary cancer and its corresponding axillary metastasis,only primary tumors positive in 7 cases,only metastasis positive in 1 case,the primary tumor and metastatic were both negative in 3 cases,The positive expression rates of CCR5 in primary cancer and its corresponding metastasis were 92%(46/50) and 80%(40/50), which shows the high homology of CCR5 in two locations.(Fisher exact test C =0.38,P=0.02).4.CCR5 and C-erbB-2 as a joint indicator of lymph node metastasisIn order to analyze the relationship between CCR5 expression and metastasis,we go further to analyzed the CCR5 with other oncogenes and tumor suppressor gene, found that CCR5 expression and oncogene C-erbB-2 was positively correlated relationship(r=0.291,p＜0.05),but has no correlation with p53,Ki-67,ER or PR. Comparison with node-negative tumor tissue,lymph node-positive tumors showed higher levels of CCR5 and C-erbB-2 cytoplasmic staining.When two biological markers was taken as indicator for evaluation respectively,the expression of CCR5 and C-erbB-2 in lymph node-positive tumors were higher than those with lymph node-negative tumors,the difference had statistical significance(CCR5:92.0% vs68.2%,P=0.026;C-erbB-2:54.0%vs 18.2%,P=0.005).When the two types of biological markers(CCR5 and C-erbB-2) were used at the same time,there were 96.0%of lymph node-positive tumors had the high-expression of at least one of a kind,and in lymph node-negative tumors,the rate was 68.2%(P=0.004).Therefore the use of two biological markers(CCR5 and C-erbB-2) increased the sensitivity of detection of lymph node metastasis comparaison with single one marker has been used in the past.【Conclusions】1.The detection of the positive expression rate of CCR5 in breast cancer was 84.72%and the positive expression rate in breast benign tumor was14%;normal breast tissue did not express CCR5.These indicated that CCR5 may be corrected with carcinogenesis and evolvement of breast cancer.2.CCR5 showed positive correction to axillary node metastasis.CCR5 may be taken as a new biological marker to predict carcinogenesis,evolvement and prognosis of breast cancer.3.C-erbB-2 had positive correction with axillary node metastasis,p53 and Ki-67,negative correction with ER and PR.CCR5 had positive correction with C-erbB-2.The combined detection of C-erbB-2 and CCR5 may do better in judging carcinogenesis,evolvement and prognosis of breast cancer.4.The interaction between CCR5 and its ligands plays an important role in carcinogenesis,evolvement and metastasis of breast cancer.CCR5 may be one of the important tumor markers to predict metastasis and prognosis,and provides a new target for breast cancer therapy.