Tissue Microarray Study Of The Role Of CXCR4, CCR7 And Their Ligands In Breast Cancer And Lymph Node Metastatic Tumor

Objectives:CXCR4, the receptor of CXCL12 or stromal cell derived factor-1(SDF-1), and CCR7, the receptor of CCL21, belong to the chemokine receptor family. They have been shown to play an important role in the migration, invasiveness, metastasis and proliferation of breast cancer cells.This study was designed to observe and study the expression of CXCR4, CCR7 and their ligands in invasive ductal breast cancer, and analyze their association with pathological features and clinical outcome.Methods:Using tissue microarray, expression of chemokine receptors CXCR4, CCR7 and their ligands SDF-1 and CCL21 in 200 invasive ductal breast cancer samples was determined by IHC(immunohistochemistry) technique. The corresponding lymph nodes and corresponding normal breast tissues in paraneoplastic were also detected. The level of CXCR4,CCR7,SDF-1 and CCL21 expression was analyzed against axillary lymph node status, clinical stage, tumor diameter, histological grade, ER status, PR status, HER-2 status. All 200 patients'follow-up information was collected for the analysis of survival rate.Results:(1) The expression level of CXCR4 in IDC was higher than that in nromal breast tissue(P<0.01); SDF-1 was highly expressed in both IDC and normal breast tissue, there was no statistically significance between the two groups(P>0.05).(2) The expression level of CXCR4 and SDF-1 in IDC with lymph node metastasis was higher than that in IDC without lymph node metastasis(P<0.01).(3)The expression level of SDF-1 in normal lymph node, primary tumor of IDC, normal breast tissue and lymph node metastatic tumor was gradually decreased(P<0.05).While the expression level of CXCR4 between primary tumor and lymph node metastatic tumor had no statistically significance(P>0.05).(4)The expression of CXCR4, SDF-1 correlated with lymph node status, HER-2 status as well as with hormone receptors negatively(both ER and PR) (P<0.05), but did not correlate with the amount of lymph nodes, age, clinical stage, tumor diameter and histological grade.(5) The expression level of CCR7 and CCL21 in IDC was higher than that in normal breast tissue(P<0.01).(6) The expression level of CCR7 and CCL21 in IDC with lymph node metastasis was higher than that in IDC without lymph node metastasis(P<0.01).(7) The expression level of CCL21 in normal lymph node, primary tumor of IDC, lymph node metastatic tumor and normal breast tissue was gradually decreased(P<0.05).While the expression level of CCR7 between primary tumor and lymph node metastatic tumor had no statistically significance(P>0.05).(8) The expression of CCR7 and CCL21 correlated with lymph node status(P<0.05), but did not correlate with the amount of lymph nodes, age, clinical stage, tumor diameter, histological grade, HER-2 status as well as with hormone receptors (both ER and PR).(9) Through correlation analysis, we discovered that CXCR4 expression was related with CCR7 expression, and SDF-1 expression correlated with CCL21 expression. But there was no correlation between chemokine receptors and their ligands.(10) Using survival analysis, we discovered that the survival rate sharply decreased in patients with high CXCR4, CCR7, SDF-1 and CCL21 expression (P<0.05).It can be concluded that CXCR4, CCR7, SDF-1 and CCL21 were important factors for prognosis of breast cancer.Conclusion:(1) The level of CXCR4 and CCR7 expression showed significant difference between IDC and normal breast tissue. Therefore, SDF-1/CXCR4 and CCL21/CCR7 may correlated with breast cancer genesis and development.(2) The expression level of CXCR4 and CCR7 was higher in breast cancer with lymph node metastasis than in those without lymph node metastasis. While their ligands SDF-1 and CCL21 were highly expressed in lymph node. This phenomenon may account for organ specific metastasis of tumor. So they can be seen as a predict factor for breast cancer metastasis. Regulating of SDF-1/CXCR4 or CCL21/CCR7 may become an target for breast cancer therapy. (3) The expression of CXCR4, CCR7 and their ligands significantly correlated with survival time of patients. So they can be seen as important index for prognosis of breast cancer patients.