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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2015, Vol. 09 ›› Issue (03) : 182 -187. doi: 10.3877/cma.j.issn.1674-0807.2015.03.006

论著

E-钙黏蛋白在乳腺癌组织中的表达及其临床意义
邓淼1, 刘江波1,†(), 刘起鹏1, 葛东峰2, 陈登庭1, 刘德纯1, 邢鲁奇2   
  1. 1.471003 洛阳,河南科技大学第一附属医院乳腺外科/乳腺疾病研究所
    2.471003 洛阳,河南科技大学第一附属医院病理科
  • 收稿日期:2015-04-09 出版日期:2015-06-01
  • 通信作者: 刘江波
  • 基金资助:
    洛阳市应用技术研究与开发基金项目(0802021A)河南科技大学第一附属医院博士科研启动基金项目项目(0801)

Expression of E-cadherin in breast cancer and its clinical significance

Miao Deng1, Jiangbo Liu1,†(), Qipeng Liu1, Dongfeng Ge2, Dengting Chen1, Dechun Liu1, Luqi Xing2   

  1. 1.Department of Breast Surgery,1Institute of Breast Diseases
    2.Department of Pathology,First Affiliated Hospital, Henan University of Science and Technology,Luoyang 471000, China
  • Received:2015-04-09 Published:2015-06-01
  • Corresponding author: Jiangbo Liu
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引用本文：

邓淼, 刘江波, 刘起鹏, 葛东峰, 陈登庭, 刘德纯, 邢鲁奇. E-钙黏蛋白在乳腺癌组织中的表达及其临床意义[J/OL]. 中华乳腺病杂志(电子版), 2015, 09(03): 182-187.

Miao Deng, Jiangbo Liu, Qipeng Liu, Dongfeng Ge, Dengting Chen, Dechun Liu, Luqi Xing. Expression of E-cadherin in breast cancer and its clinical significance[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2015, 09(03): 182-187.

目的

研究上皮细胞黏附分子E-钙黏蛋白(E-cadherin)在乳腺癌组织中的表达和临床意义。

方法

回顾性分析2009 年11 月至2014 年10 月在河南科技大学第一附属医院接受改良根治术的303 例乳腺癌病例资料,应用免疫组织化学染色法检测癌组织中E-cadherin 和HER-2 的表达,分析E-cadherin 在不同分子分型乳腺癌中的表达特点及与临床病理特征的相关性。 计数资料采用χ2 检验或Fisher 确切概率法,相关性分析采用Pearson 相关分析,并用Logistic 回归分析影响E-cadherin 表达的独立因素。

结果

303 例乳腺癌组织中E-cadherin 和HER-2 阳性表达率分别为71.9% (218/303)和16.2%(49/303)。 E-cadherin 与患者年龄、月经状态、TNM 分期及腋窝淋巴结转移有关(χ2 =4.854、8.277、8.757、10.614,P 均＜0.050),HER-2 表达与组织学分级有关(χ2=0.002,P＜0.050)。 Pearson 相关分析显示,乳腺癌组织中E-cadherin 与HER-2、ER 及PR 呈正相关(r=0.135、0.206、0.135,P=0.019、0.000、0.019),而与Ki67 表达强度无关;HER-2 与ER、PR 呈负相关(r=-0.160、-0.118,P=0.005、0.040),与Ki67 表达呈正相关(r=0.228,P=0.000)。 Logistic 回归多因素分析显示年龄、肿瘤直径、TNM 分期为影响E-cadherin 表达的临床病理因素,而HER-2 和ER 是影响E-cadherin 表达的分子病理因素。 E-cadherin 阳性表达率在不同分子分型间差异有统计学意义(χ2=24.816,P=0.000),而三阴性乳腺癌(TNBC)为51.3%,显著低于luminal B 型及HER-2 过表达型(P 均＜0.008)。

结论

E-cadherin 表达缺失与TNBC 更容易发生侵袭转移密切相关,而HER-2 和ER 可能参与E-cadherin 表达缺失的调控机制。

关键词: 乳腺肿瘤, E-钙黏蛋白, 分子亚型, 表皮生长因子受体

Objective

To study the expression of epithelial cellular adhesion molecule (E-cadherin)in different molecular subtypes of breast cancer and its clinical significance.

Methods

A total of 303 cases of breast cancer treated with modified radical mastectomy were retrospectively collected in the First Affiliated Hospital, Henan University of Science and Technology from November 2009 to October 2014.The expressions of E-cadherin and HER-2 in breast cancer tissues were detected by immunohistochemical staining to analyze the expression pattern of E-cadherin in different molecular subtypes of breast cancer and its association with clinicopathological features of the patients.Numeration data was processed using χ2 test or Fisher's exact test,correlation analysis was performed using Pearson method, and Logistic regression was used to analyze the independent factors in E-cadherin expression.

Results

The positive rates of E-cadherin and HER-2 in 303 cases of breast cancer were 71.9% (218/303) and 16.2% (49/303) respectively.E-cadherin expression was correlated with patients' age, menopausal status, TNM staging, and axillary lymph node metastasis (χ2 =4.854,8.277,8.757,10.614,all P ＜0.050);and HER-2 expression was associated with histological grade(χ2=0.002,P＜0.050).Pearson correlation analysis showed that E-cadherin was positively correlated with HER-2, ER, and PR in breast cancer tissue (r=0.135,0.206,0.135, P=0.019,0.000,0.019), and not correlated with Ki67.HER-2 was negatively correlated with ER and PR (r=-0.160, -0.118, P=0.005,0.040), and positively correlated with Ki67 (r=0.228, P=0.000).Logistic regression showed that patients'age, tumor size, and TNM staging, clinico pathological and HER-2 and ER were molecular pathological factors influencing E-cadherin expression in breast cancer.There was a significant difference in E-cadherin expression between different molecular subtypes of breast cancer (χ2 = 24.816, P = 0.000).The positive rate of E-cadherin expression was 51.3% in triple-negative breast cancer (TNBC), significantly lower than that in luminal B or HER-2-riched (all P ＜0.008).

Conclusion

The deficiency of E-cadherin expression is associated with the biological behaviors of invasion and metastasis in TNBC, while HER-2 and ER may be involved in the regulatory mechanism of E-cadherin expression deficiency.

Key words: Breast neoplasms, E-cadherin, Molecular subtypes, Epidermal growth factor receptor
表1 影响乳腺癌E-cadherin 表达的临床病理因素Logistic 回归变量赋值表
变量 变量分类及赋值
E-cadherin表达 阴性=1,阳性=2
年龄 ＜50岁=1,≥50岁=2
月经状态 绝经前=1,绝经后=2
组织学分级 Ⅰ级=1,Ⅱ级=2,Ⅲ级=3
腋窝淋巴结转移 N0=1,N1=2,N2=3,N3=4
肿瘤直径 T1=1,T2=2,T3=3
TNM分期 Ⅰ期=1,Ⅱ期=2,Ⅲ期=3,Ⅳ期=4
表2 影响乳腺癌E-cadherin 表达的分子病理因素Logistic 回归变量赋值表
变量 变量分类及赋值
E-cadherin表达 阴性=1,阳性=2
HER-2表达 阴性=1,阳性=2
ER表达 阴性=1,阳性=2
PR表达 阴性=1,阳性=2
Ki67表达 阴性=1,阳性=2
图1 E-钙黏蛋白和HER-2 蛋白在乳腺浸润性导管癌组织中的表达情况(SP ×200) 注:a 图所示E-钙黏蛋白在乳腺癌中阳性表达;b 图所示HER-2 在乳腺癌中阳性表达
表3 303 例乳腺癌临床病理特征与E-钙黏蛋白(E-cadherin)和HER-2 表达之间的关系
临床病理特征 例数 E-cadherin(例) χ2值 P值 HER-2(例) χ2值 P值
阴性 阳性 阴性 阳性
年龄
＜50岁 144 49 95 4.854 0.028 125 19 1.794 0.180
≥50岁 159 36 123 129 30
月经状态a
绝经前 170 59 111 8.277 0.004 142 28 0.017 0.896
绝经后 132 26 106 111 21
组织学分级b
Ⅰ级+Ⅱ级 210 47 163 2.295 0.130 167 43 6.786 0.009
Ⅲ级 63 20 43 59 4
肿瘤直径c
≤2cm 97 23 74 0.001 0.974 82 15 0.002 0.962
＞2cm 153 36 117 129 24
TNM分期d
Ⅰ期 57 15 42 8.757 0.033 50 7 0.731 0.866
Ⅱ期 121 22 99 101 20
Ⅲ期 45 10 35 38 7
Ⅳ期 27 12 15 22 5
淋巴结转移
N0 146 45 101 10.614 0.014 127 19 4.084 0.253
N1 79 15 64 61 18
N2 52 12 40 45 7
N3 26 13 13 21 5
表4 乳腺癌组织中E-cadherin 表达与临床病理特征关系的Logistic 多因素回归分析
因素 回归系数 标准误 Wald值 P值 OR值 95%CI
年龄 0.775 0.347 4.996 0.025 2.171 1.100～4.284
肿瘤直径 0.796 0.386 4.257 0.039 2.217 1.041～4.724
TNM分期 -0.581 0.214 7.333 0.007 0.560 0.368～0.852
常量 1.416 1.023 1.916 0.166 4.120
表5 303 例乳腺癌组织中E-钙黏蛋白(E-cadherin)和HER-2 表达与ER、PR 及Ki67 表达的相关性
分子指标 例数 E-cadherin(例) r值 P值 HER-2(例) r值 P值
阴性 阳性 阴性 阳性
HER-2
阴性 254 78 176 0.135 0.019
阳性 49 7 42
ERa
阴性 113 45 68 0.206 0.000 86 27 -0.160 0.005
阳性 188 39 149 166 22
PRb
阴性 163 55 108 0.135 0.019 130 33 -0.118 0.040
阳性 139 30 109 123 16
Ki67c
阴性 90 32 58 0.113 0.051 87 3 0.228 0.000
阳性 212 52 160 166 46
表6 乳腺癌E-钙黏蛋白表达与分子病理特征关系的Logistic 多因素回归分析
因素 回归系数 标准误 Wald值 P值 OR值 95%CI
HER-2 1.089 0.454 5.762 0.016 2.972 1.221～7.231
ER 1.095 0.277 15.642 0.000 2.989 1.737～5.144
常量 -2.115 0.720 8.635 0.003 0.121
表7 E-钙黏蛋白(E-cadherin)在不同分子分型乳腺癌中的表达a
分子分型 例数 E-cadherin
阴性(例) 阳性(例) 阳性率(%)
luminal A 42 11 31 73.8cde
luminal Bb 146 28 118 80.8fg
HER-2过表达 27 4 23 85.2h
TNBC 78 38 40 51.3
χ2值 24.816
P值 0.000
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