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


METHODS
AGR2 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.


RESULTS
The 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).


CONCLUSIONS
The 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.
Wu
Zheng-sheng
ZS
Department of Pathology, Anhui Medical University, Hefei 230032, China.
Wu
Qiang
Q
Ding
Xiang-dong
XD
Wang
Hong-qun
HQ
Shen
Yu-xian
YX
Fang
Sheng-yun
SY
D018931:Antineoplastic Agents, Hormonal / Q000032:analysis; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009088:Mucoproteins; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D009367:Neoplasm Staging; D015513:Oncogene Proteins; D011379:Prognosis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C502296:AGR2 protein, human