雄激素受体表达与乳腺癌病理类型及分子生物学关系的研究

Relationship between androgen receptor expression and breast cancer pathology type and molecular biology

目的目前国内外研究证实,雄激素受体(androgen receptor,AR)在乳腺正常组织及癌组织中均有表达,在乳腺癌中的作用机制及其与乳腺癌临床病理特征及生存预后关系尚不完全明了,原因之一是AR检测方法和截断值不同,以及对雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)等表达判定标准不完全一致所致。本研究按照2015年《乳腺癌雌、孕激素受体免疫组织化学检测指南》的判定标准,应用免疫组织化学法检测乳腺癌患者相关标志物的表达,并探讨乳腺癌组织中AR的表达与乳腺癌病理类型与分子生物学关系。方法选取山东大学附属山东省肿瘤医院乳腺病防治中心单一治疗组2014-04-01-2016-12-31连续收治来自山东地区的221例原发性浸润性乳腺癌患者作为研究对象。采用免疫组化染色法检测乳腺癌组织中AR、ER、PR、人表皮生长因子受体2(human epidermal growth factor receptor-2,HER2)和Ki-67的表达情况,并结合患者发病年龄、肿瘤大小、淋巴结受累、TNM分期及肿瘤组织学分级等临床病理指标进行分析。结果 221例乳腺癌组织中AR阳性率为74.7%。≤35岁的乳腺癌患者AR阳性率为55.6%,>35岁的AR阳性率为71.1%;肿瘤最大径≤2cm AR阳性率为77.4%,肿瘤最大径2~5cm AR阳性率为74.5%,肿瘤最大径≥5cm AR阳性率为80.0%;腋窝淋巴结有转移AR阳性率为77.5%,腋窝淋巴结无转移AR阳性率为75.2%;肿瘤组织学Ⅰ级AR阳性率为74.3%,组织学Ⅱ级AR阳性率为77.6%,组织学Ⅲ级AR阳性率为72.9%。AR阳性率与发病年龄、肿瘤大小、组织学分级及腋窝淋巴结状态均无相关性,均P值>0.05。ER阳性乳腺癌组织中AR阳性率为82.0%,ER阴性乳腺癌组织中AR阳性率为57.4%;PR阳性乳腺癌组织中AR阳性率为85.8%,PR阴性乳腺癌组织中AR阳性率为63.8%。HER2阳性乳腺癌组织中AR阳性率为86.8%,HER2阴性乳腺癌组织中AR阳性率为71.0%。Ki-67高表达乳腺癌组织中AR阳性率为74.1%,Ki-67低表达乳腺癌组织中AR阳性率为70.3%。AR阳性率与ER、PR和HER2的状况均显著相关,P<0.01。分子分型后发现,乳腺腔内A型(Luminal A型)乳腺癌AR阳性率为76.9%,乳腺腔内B型(Luminal B型)AR阳性率为82.5%,HER2阳性型AR阳性率为71.4%,三阴性乳腺癌(triplenegative breast cancer,TNBC)AR阳性率为50.0%,表明不同分子亚型AR表达率差异有统计学意义,P<0.05。结论乳腺癌组织AR阳性率与ER、PR和HER2表达均呈显著正相关,AR在Luminal型乳腺癌组织阳性率明显高于TNBC组织,提示AR的功能很大程度上取决于受体阳性乳腺癌中ER的表达。

OBJECTIVE Research confirmed that androgen receptors（AR） in breast cancer and normal tissue wereexpressed, mechanism of action in breast cancer and its relationship with clinical pathological characteristics and survival prognosis of breast cancer is not yet fully understood. One of the reasons is that the AR detection method and the cut of the date are are different, and the criterion for the expression of ER and PR is not completely consistent. This study aimed to explore the relationship between androgen receptor expression and breast cancer pathology type and molecular biology. METHODS Using immunohistochemical staining method to detect AR, estrogen receptors （ER） , progesterone receptor （PR） and human epidermal growth factor receptor 2 （HER2）, cell proliferating nuclear antigen （Ki-67） expression in 221 breast cancer tissue and combined with the onset of patient age, tumor size, lymph node involvement, TNM stage,histo- logical grade and other clinical cancer pathological index. RESULTS The AR positive rate was 74.7% in 221 breast canc- er tissues. The ratio of AR of 35 year-old was 55.6% ,while that of 〉 35-year-old AR was 71.1%. AR positive rate in the maximum diameter of tumor less than 2 cm was 77.4~, and AR positive rate in the maximum diameter 2--5 cm was 74.5%. AR positive rate was 80.0% in the maximum diameter of tumor greater than 5 cm. AR positive rate was 77.6% in axillary lymph node with metastasis and 75. 20//00 in axillary lymph node without metastasis. AR positive rate was 74.30//00 in tumor histologic grade I , 77.6~ in histologic grade II , and 72.9% in histologic grade HI. There was no cor- relation between AR positive rate and onset age, tumor size, histological grade and axillary lymph node status（P^0.05）. The AR positive rate of ER positive breast cancer was 82.0%. The rate of PR positive breast cancer was 85.8%. The rate of HER2 positive breast cancer was 86. 8%, and AR positive rate was significantly correlated with ER, PR and HER2. The positive rate of AR in Ki-67 high expresses breast cancer tissue was 74.1~, and the rate of AR in Ki-67 low expression breast cancer tissues was 70.3~. We found that after molecular typing, Luminal type A breast cancer AR positive rate was 76.90//00, Luminal B breast cancer AR positive rate was 82.5%, positive HER2 type AR positive rate was 71.4%, three negative breast cancer （TNBC） AR positive rate was 50.0%, which showed that there were differ- ences between the different molecular subtypes and AR expression rate （P%0.05）. CONCLUSIONS AR positive rate is positively correlated with the expression of ER, PR and HER2. The positive rate of AR in Luminal breast cancer is sig- nificantly higher than that of TNBC. The function of AR is largely dependent on the expression of ER in receptor-positive breast cancer.