OBJECTIVETo investigate the expression of a novel metastasis-inducing protein human anterior gradient-2 (AGR2) in breast cancer and its clinical and prognostic significance.

METHODSAGR2 expression was assessed in 160 cases of breast cancer and 20 cases of benign breast diseases by immunohistochemistry using tissue chip technology. In addition the expression of ERa, PR and c-erbB-2 in breast cancer was also evaluated. Follow-up information of 5-year duration was available in 127 patients with breast cancer. Kaplan-Meier analysis and COX regression model were used to analyze the correlation between AGR2 expression and the follow-up clinical data.

RESULTSThe expression of AGR2 was significantly higher in breast cancers than that in benign diseases (68.3% vs. 25.0% , P < 0.01). There was a negative correlation between AGR2 expression and the histological grade of breast cancer (P <0.05) , whereas positive correlations was found between the expression of AGR2 and ERalpha (P <0.05), and between the expression of AGR2 and PR (P <0.01). In the subgroup of ERalpha-positive breast cancer, Logistic regression model demonstrated AGR2 and TNM stage were important factors affecting lymph node metastasis (both P < 0.01). Kaplan-Meier analysis demonstrated that a positive expression of AGR2 was associated with poor overall survival and relapse-free survival (both P <0.01). Moreover, COX regression model confirmed the expression of AGR2 as an independent prognostic factor among patients with ERa-positive breast cancer (P <0.01).

CONCLUSIONSThe abnormal expression of AGR2 may play a role in the pathogenesis and progression of breast cancer. The metastasis-inducing capability of AGR2 may be partly regulated through the ER pathway. Therefore, AGR2 may be a useful molecular marker for prognostication for patient with hormone-responsive breast cancer.