The Expression And Significance Of CXCR4 Receptor In Human Breast Cancer

Objective:CXCR4, the receptor for CXCL12 or stromal cell-derived factor-1 a(SDF-1a), belongs to the chemokine receptor family and has 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 and its association with pathological features and clinical outcome in human breast cancer. Methods:Expression of CXCR4 in 23 breast mild ductal hyperplasia, 26 severe atypical ductal hyperplasia, 32 DCIS (ductal carcinoma in situ) and 126 invasive cancer samples were determined by IHC (immunohistoch-emistry) technique, respectively. The level of CXCR4 expression in 126 invasive cancers was analyzed against tumor type, axillary lymph node status, tumor diameter, cTNM stage, histological grade, ER status, PR status, HER-2 status, P53 status, PCNA status, metastasis and survival over a median 144 months follow-up period. Results:The percentage of CXCR4 positively expression increased from mild ductal hyperplasia (8. 70%) to atypical ductal hyperplasia (23. 08%) to DCIS (56.25%) to invasive cancer (60.32%), (P<0.05). While, there was no significant difference of CXCR4 expression between DCIS and invasive cancer. CXCR4 positively expression in invasive breast cancer was related with lymph nodal status, cTNM stages, HER-2 status and PCNA status positively, as well as with hormone receptor negatively (both ER and PR), and was not related with tumor diameter, histological gradeand P53 status. The level of CXCR4 expression showed a significant difference between lymph node-positive group and node-negative group (48.94% vs. 67.09%, respectively, P<0.05). Among the 126 invasive breast cancer, 57 happened far metastasis and the other 69 did not during the follow-up period, and the level of CXCR4 expression of far metastasis group higher than that of non-far metastasis group. The overall survival rate in CXCR4 positive groups are higher than that in CXCR4 negative group. RR in weak, moderate and strong CXCR4 expression group is 5.315, 7.417, 15.868 respectively by COX proportional hazard regression model. Conclusion:The level of CXCR4 expression showed no significant difference between DCIS and invasive cancer, so CXCR4 may be a marker in early stage of breast tumorigenesis. CXCR4 expression is associated with breast tumor progression, suggesting potential value as a diagnostic marker. The patients with CXCR4 positive invasive breast cancer happened more far metastasis, therefore CXCR4 may be a factor to predict metastasis. CXCR4 may be a useful prognostic indicator and a potential therapeutic target in cancer therapies in patients with breast cancer.