上皮-间质转化的生物学标志物在食管腺癌中的作用：一项免疫组织化学研究

The role of biological markers of epithelial to mesenchymal transition in oesophageal adenocarcinoma, an immunohistochemical study.

作者信息

Prins M J D, Ruurda J P, Lolkema M P, Sitarz R, Ten Kate F J W, van Hillegersberg R

机构信息

Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands.

出版信息

J Clin Pathol. 2015 Jul;68(7):529-35. doi: 10.1136/jclinpath-2015-202962. Epub 2015 Apr 8.

DOI:10.1136/jclinpath-2015-202962

PMID:25855799

Abstract

BACKGROUND

E-cadherin, β-catenin, epidermal growth factor receptor (EGFR), neuronal cadherin (N-cadherin) and Cyclin D1 are involved in epithelial to mesenchymal transition (EMT). However, the prognostic significance of EMT markers in oesophageal adenocarcinoma (OAC) is unknown. Aim of this study was to evaluate the prognostic value of, and the association between different EMT markers in OAC.

METHODS

Tumour cores of 154 patients with OAC were included in a tissue microarray. Scoring criteria was based on immunohistochemical staining intensity.

RESULTS

EMT-associated markers were expressed in OAC: reduced membranous E-cadherin and β-catenin were seen in 11.4% and 51.7%, nuclear β-catenin in 19.1% and EGFR and Cyclin D1 overexpression in 56.5% and 27.4% of tumours. Mesenchymal marker N-cadherin was not expressed in OAC. A positive correlation was seen between membranous β-catenin and E-cadherin expression (R=0.209, p=0.001) and between EGFR and Cyclin D1 (R=0.257, p=0.002). In univariate analysis, EGFR overexpression and membranous β-catenin staining were significantly associated with a poor survival (HR 2.145; 95% CI 1.429 to 3.218, p<0.001 and HR 1.665; 95% CI 1.114 to 2.488; p=0.013). However, Cyclin D1 (HR 1.092; 95% CI 0.702 to 1.698; p=0.697), nuclear β-catenin (HR 1.322; 95% CI 0.799 to 2.189; p=0.277) and E-cadherin (HR 1.012; 95% CI 0.554 to 1.851; p=0.968) were not associated with survival. In multivariate analysis, EGFR overexpression was an independent prognostic factor for poor survival (HR 1.678; 95% CI 1.055 to 2.668; p=0.029) together with T stage (HR 2.759; 95% CI 1.356 to 5.576; p=0.005).

CONCLUSIONS

This study supports the presence of EMT in OAC. Moreover, EGFR overexpression was independently associated with a poor survival.

摘要

背景

E-钙黏蛋白、β-连环蛋白、表皮生长因子受体（EGFR）、神经钙黏蛋白（N-钙黏蛋白）和细胞周期蛋白D1参与上皮-间质转化（EMT）。然而，EMT标志物在食管腺癌（OAC）中的预后意义尚不清楚。本研究的目的是评估OAC中不同EMT标志物的预后价值及其之间的关联。

方法

154例OAC患者的肿瘤组织芯被纳入组织芯片。评分标准基于免疫组织化学染色强度。

结果

EMT相关标志物在OAC中表达：11.4%的肿瘤中膜性E-钙黏蛋白减少，51.7%的肿瘤中β-连环蛋白减少，19.1%的肿瘤中β-连环蛋白核表达，56.5%的肿瘤中EGFR过表达，27.4%的肿瘤中细胞周期蛋白D1过表达。间质标志物N-钙黏蛋白在OAC中未表达。膜性β-连环蛋白与E-钙黏蛋白表达之间呈正相关（R=0.209，p=0.001），EGFR与细胞周期蛋白D1之间呈正相关（R=0.257，p=0.002）。在单因素分析中，EGFR过表达和膜性β-连环蛋白染色与较差的生存率显著相关（HR 2.145；95%CI 1.429至3.218，p<0.001；HR 1.665；95%CI 1.114至2.488；p=0.013）。然而，细胞周期蛋白D1（HR 1.092；95%CI 0.702至1.698；p=0.697）、β-连环蛋白核表达（HR 1.322；95%CI 0.799至2.189；p=0.277）和E-钙黏蛋白（HR 1.012；95%CI 0.554至1.851；p=0.968）与生存率无关。在多因素分析中，EGFR过表达与T分期（HR 2.759；95%CI 1.356至5.576；p=0.005）一起是生存率差的独立预后因素（HR 1.678；95%CI 1.055至2.668；p=0.029）。