一种新型转移诱导蛋白AGR2在乳腺癌中的表达及其临床和预后意义

目的 研究转移诱导蛋白AGR2在人乳腺癌中表达和意义及其与患者预后的关系.方法 采用组织芯片,应用免疫组织化学方法检测160例乳腺癌和20例乳腺良性病变组织AGR2表达,以及乳腺癌ERα、PR和HER2表达状况,并用Kaplan-Meier曲线法和Log-rank检验对有随访资料的127例进行与AGR2的相关性分析.结果 乳腺癌AGR2表达量较乳腺良性病变显著性增高(68.3%和25.0%,P＜0.01);AGR2表达与乳腺癌组织学分级呈负相关(P＜0.05),与乳腺癌ERα和PR表达呈正相关(分别为P＜0.05和P＜0.01);Logistic回归模型显示AGR2和TNM分期是ERa阳性乳腺癌淋巴结转移重要的影响因子(均P＜0.01);Kaplan-Meier生存曲线显示ERα阳性乳腺癌患者中,AGR2阳性患者总生存率和无复发生存率均显著低于阴性患者(均P＜0.01),COX比例风险模型分析也证实AGR2蛋白表达是ERα阳性乳腺癌患者独立的预后影响因子(P＜0.01).结论 AGR2表达异常可能参与了乳腺癌的发生、发展过程,该机制可能部分依赖雌激素受体途径发挥其诱导肿瘤转移作用.AGR2可能是一个潜在的分子标记物,对雌激素受体阳性乳腺癌患者的预后评估有一定提示作用.

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.