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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (03) : 146 -150. doi: 10.3877/cma.j.issn.1674-0807.2016.03.005

论著

雄激素受体表达程度与乳腺癌预后的关系
阎语1, 玉素甫·买买提1, 王昶文1, 谭捷1, 赵萩阳1, 黄韬1,†()   
  1. 1.430022 武汉,华中科技大学同济医学院附属协和医院甲状腺乳腺外科
  • 收稿日期:2015-10-25 出版日期:2016-06-01
  • 通信作者: 黄韬
  • 基金资助:
    华中科技大学自主创新基金-校长基金(0118530088)

Correlation analysis of androgen receptor expression with breast cancer prognosis

Yu Yan1, Changwen Wang1, Jie Tan1, Qiuyang Zhao1, Tao Huang1,†()   

  1. 1.Department of Breast and Thyroid Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430022, China
  • Received:2015-10-25 Published:2016-06-01
  • Corresponding author: Tao Huang
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阎语, 玉素甫·买买提, 王昶文, 谭捷, 赵萩阳, 黄韬. 雄激素受体表达程度与乳腺癌预后的关系[J/OL]. 中华乳腺病杂志(电子版), 2016, 10(03): 146-150.

Yu Yan, Changwen Wang, Jie Tan, Qiuyang Zhao, Tao Huang. Correlation analysis of androgen receptor expression with breast cancer prognosis[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(03): 146-150.

目的

探讨乳腺癌中雄激素受体(AR)的表达程度与乳腺癌临床病理特征及乳腺癌预后的关系。

方法

通过组织芯片(购自上海芯超生物科技有限公司,芯片号:K14-051)收集2001 年1 月至2008 年7 月期间接受乳腺癌改良根治术的310 例乳腺浸润性导管癌患者的病例资料,应用免疫组织化学技术检测癌组织中AR 的表达,并采用χ2 检验比较患者年龄、淋巴结转移情况及ER、P53、Ki67 表达情况与AR 表达程度的关系,采用非参数秩和检验比较患者分子分型、肿瘤大小、乳腺癌组织学分级与AR 表达程度的关系,绘制Kaplan-Meier 生存曲线研究AR 表达程度对乳腺癌患者预后的影响,并用Cox比例风险回归模型探讨影响乳腺癌患者预后的独立因素。

结果

AR 阳性表达、弱阳性表达、阴性表达患者分别为155、100、55 例,所占比例为50%(155/310)、32%(100/310)、18%(55/310)。 AR 的表达程度与患者年龄、分子分型、组织学分级、ER 及P53 表达程度有关(χ2=7.128,P=0.028;Z=56.099,P＜.001;Z=10.144,P=0.006;χ2 =65.577,P＜.001;χ2 =16.127,P＜.001)。 Kaplan-Meier 生存分析显示,不同AR 表达程度的患者间OS 率差异有统计学意义(χ2 =11.965,P=0.003),其中AR 阳性表达(81.3%)、AR 弱阳性表达组(87.0%)OS 率均高于AR 阴性表达组(67.3%)(χ2 =5.991,P=0.014;χ2=10.335,P=0.001),而AR 阳性表达组与AR 弱阳性表达组比较,OS 率差异无统计学意义(χ2 =2.386,P=0.122)。 Cox 回归分析显示,AR、肿瘤大小、淋巴结状态以及分子分型是乳腺癌预后的独立预测因素(OR=0.559,95%CI:0.318 ～0.981,P=0.043;OR=1.505,95%CI:1.047 ～2.161,P=0.027;OR=1.616,95%CI:1.046 ～2.497,P=0.030;OR=1.457,95%CI:1.023 ～2.076,P=0.037)。

结论

AR 表达程度与乳腺癌预后有关,可作为其不良预后的独立预测因子。

关键词: 乳腺肿瘤, 受体, 雄激素, 免疫组织化学, 预后

Objective

To investigate the relationship of androgen receptor (AR) expression with clinicopathological characteristics and the prognosis of breast cancer.

Methods

Using tissue microarray(purchased from Shanghai Xinchao Biotechnological Co., Ltd., No. K14-051), we collected the data of 310 patients with breast invasive ductal carcinoma who underwent modified mastectomy from January 2001 to July 2008. The expression of AR was detected by immunohistochemistry. The relationship of AR expression with patients' age, lymphatic metastasis, ER, P53, and Ki67 expression was analyzed using χ2 test. The relationship of AR expression with molecular subtype, tumor size and histological grade was analyzed by nonparametric rank sum test. The Kaplan-Meier survival curve was used to investigate the impact of AR on breast cancer prognosis, and Cox regression model was used to explore independent factors in the prognosis of breast cancer.

Results

In all 310 patients, there were 155 patients with AR positive, 100 AR weakly positive,55 AR negative, accounting for 50%, 32% and 18% respectively. AR expression was correlated with patients' age, molecular subtype, histological grade, ER, and P53 expression (χ2 =7.128, P=0.028;Z=56.099,P＜0.001; Z=10.144, P=0.006; χ2=65.577,P＜0.001; χ2=16.127,P＜0.001). There was a significant difference in overall survival among three groups with different AR expression (χ2=11.965, P=0.003). The overall survival in AR positive group(81.3%)or AR weakly positive group ( 87.0%) was significantly higher than that in AR negative group(67.3%) (χ2 =5.991, P=0.014;χ2 =10.335, P=0.001), while the overall survival showed no statistical difference between AR positive group and AR weakly positive group (χ2=2.386, P=0.122). Cox regression showed that AR, tumor size, lymph node status and molecular subtypes were the independent predictive factors in the prognosis of breast cancer (OR=0.559,95%CI:0.318-0.981,P=0.043;OR=1.505,95%CI:1.047-2.161,P=0.027;OR=1.616,95%CI:1.046-2.497, P = 0.030; OR = 1.457, 95% CI: 1.023-2.076, P = 0.037).

Conclusion

AR expression is associated with the prognosis of breast cancer, so it can be used as an independent predictive factor in the prognosis of breast cancer.

Key words: Breast neoplasms, Receptor, androgen, Immunohistochemistry, Prognosis
表1 影响乳腺癌中AR 表达的临床病理因素赋值表
变量 变量分类及赋值
年龄 ＜50岁=0,≥50岁=1
肿瘤大小 T1=1,T2=2,T3～4=3
淋巴结转移 无=0,有=1
组织学分级 1级=1,2级=2,3级=3
分子分型 luminal A=1,luminal B=2,HER-2过表达=3,三阴性=4
ER 阴性=0,阳性=1
HER-2 阴性=0,阳性=1
AR 阴性=0,阳性=1
Ki67 ＜14%=0,≥14%=1
P53 阴性=0,阳性=1
表2 310 例浸润性乳腺癌组织AR 表达与临床病理特征的关系
临床病理特征 例数 AR表达(例) 检验值 P值
阳性 弱阳性 阴性
年龄
＜50岁 110 44 41 25 χ2=7.128 0.028
≥50岁 200 111 59 30
分子分型
luminal A 136 12 50 74 Z=56.099 ＜0.001
luminal B 75 3 21 51
HER-2过表达 36 6 13 17
三阴性 63 34 16 13
肿瘤大小
T1 79 43 24 12 Z=4.442 0.109
T2 197 102 63 32
T3～4 34 10 13 11
淋巴结转移
无 146 74 41 31 χ2=1.045 0.307
有 164 81 59 24
组织学分级
1级 48 19 23 6 Z=10.144 0.006
2级 236 127 71 38
3级 26 9 6 11
ER
阴性 109 34 30 45 χ2=65.577 ＜0.001
阳性 201 121 70 10
P53
阴性 91 32 44 15 χ2=16.127 ＜0.001
阳性 219 123 56 40
Ki67
≥14% 99 47 28 24 χ2=4.362 0.113
＜14% 211 108 72 31
图1 AR 在乳腺癌组织中表达的免疫组织化学染色结果 注:AR 为雄激素受体;a 图为AR 表达的阴性对照(SP ×400);b 图为AR 阴性表达(SP ×400);c 图为AR 弱阳性表达(SP ×400);d 图为AR 阳性表达(SP ×400)
图2 不同AR 表达乳腺癌患者的生存曲线比较 注:AR 为雄激素受体;AR 阳性表达(81.3%)、AR 弱阳性表达组(87.0%)OS 率均高于AR 阴性表达组(67.3%),χ2 =5.991、10.335,P=0.014、0.001;AR 阳性表达组与AR 弱阳性表达组比较,OS 率差异无统计学意义,χ2=2.386,P=0.122
表3 浸润性乳腺癌中AR 表达与临床病理特征关系的Cox 多因素回归分析(n=310)
临床病理特征 回归系数 标准误 Wald值 P值 OR值 95%置信区间
分子分型 0.377 0.180 4.353 0.037 1.457 1.023～2.076
肿瘤大小 0.409 0.185 4.887 0.027 1.505 1.047～2.161
淋巴结转移 0.480 0.222 4.683 0.030 1.616 1.046～2.497
AR -0.582 0.287 4.101 0.043 0.559 0.318～0.981
ER 0.576 0.454 1.610 0.204 1.780 0.731～4.335
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