ER和PR阴性乳腺癌雄激素受体与HER2表达相关性及其临床意义

Evaluation of the clinical significance of androgen receptor expression in hormone receptor-negative breast cancer with different HER2status

目的激素受体阴性(ER-/PR-)乳腺癌具有明显的肿瘤异质性,临床治疗手段相对有限。本研究探讨激素受体阴性乳腺癌组织中,雄激素受体(androgen receptor,AR)和HER2表达的相关性,及其与临床病理参数和预后的相关性。方法收集中国人民解放军福州总医院经手术治疗并病理确诊的乳腺癌120例,中位年龄52岁。采用FISH法检测收集的激素受体阴性乳腺癌组织HER2/neu基因状态,分为HER2阳性(HER2过表达组)和HER2阴性(三阴组)两组,每组60例。并采用EliVisionTMplus免疫组化法检测AR、Ki-67、EGFR表达,分析HER2和AR表达与临床病理参数、3年无病生存期(disease free survival,DFS)的相关性。结果 AR在激素受体阴性乳腺癌组织阳性率为61.67%(74/120),HER2过表达组和三阴组分别为73.33%(44/60)和50.00%(30/60)。激素受体阴性乳腺癌组织中,AR表达与月经状态、肿瘤大小、组织学分级、EGFR表达及HER2状态相关,均P值<0.05;在HER2过表达组中,AR表达与月经状态、淋巴结受累、EGFR表达相关,均P值<0.05;三阴组中,AR表达与肿瘤大小和组织学分级相关,均P值<0.05。Kaplan-Meier法分析显示,HER2过表达组中AR表达与患者的3年DFS呈正相关,P<0.05;Cox回归法分析结果示,肿瘤大小、淋巴结受累、EGFR表达、AR表达均与患者的3年DFS有关,P<0.05。结论 AR可能成为筛选激素受体阴性乳腺癌高危人群和预测其预后的辅助指标之一,可作为激素受体阴性乳腺癌的新治疗靶点,为不同HER2状态乳腺癌治疗提供新思路。

OBJECTIVE Hormone receptor-negative breast cancer not only has obvious tumor heterogeneity,but its clinical treatment is relatively limited.Androgen receptor（AR）is widely expressed in breast cancer and it may be a potential prognostic factor.This study was to investigate the correlation between the expression of AR and the clinicopathologic characteristics as well as survival prognosis in hormone receptor-negative breast cancer of various HER2 statuses.METHODS Totally 120 patients with breast cancer diagnosed by pathology were recruited from Fuzhou General Hospital of PLA,and their median age was 52 years.The gene copy number of HER2/neu were examined by fluorescent in situ hybridization（FISH）from collected hormone receptor-negative breast cancer tissues.Totally 60 HER2（-）cases and 60HER2（＋）cases were respectively allocated into two groups：HER2over-expression group and triple negative group.The protein expression level of AR,Ki-67,EGFR in 120 cases were assayed using immunohistochemistry.The relationships between AR expression and clinicopathologic features and 3years-DFS were also analyzed.RESULTS The positive rate of AR was 61.67%（74/120）,and the rate of AR expression was 73.33%（44/60）and 50.00%（30/60）in the HER2-positive and HER2-negative cases,respectively.The AR expression was correlated with postmenopausal status,small tumor size,low histological grade of the tumor,EGFR-negative expression and HER2 gene amplification（P〈0.05）.The expression of AR was associated with menstrual status,lymph node metastasis and the status of EGFR in HER2-positive cases（P〈0.05）,positive correlated with tumor size and histological grade in HER2-negative cases（P〈0.05）.Kaplan-Meier analysis data showed that AR-positive group had a more favorable prognosis（P〈0.05）,this result was also found among patients with HER2-positive tumor（P〈0.05）.The multivariate analysis indicated that tumor size,lymph node metastasis,TNM stage and AR expression were independent prognostic factors influencing 3-year DFS of ER-/PR- breast cancer（P〈0.05）.CONCLUSIONS AR is expressed in a great number of hormone receptor-negative breast cancer of various HER2 status and it shows significant correlation with clinical hormone therapy and pathologic prognostic factors.AR plays a potential role in the clinical management of women patients with hormone receptor-negative breast cancer.