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白细胞黏附-GPCR EMR2 在人类乳腺癌中异常表达,并与患者生存相关。

Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival.

机构信息

Sir William Dunn School of Pathology, University of Oxford, The Nuffield Department of Clinical Laboratory Sciences and Molecular Oncology, John Radcliffe Hospital, Oxford, UK.

出版信息

Oncol Rep. 2011 Mar;25(3):619-27. doi: 10.3892/or.2010.1117. Epub 2010 Dec 21.

DOI:10.3892/or.2010.1117
PMID:21174063
Abstract

EGF-like module containing mucin-like hormone receptor 2 (EMR2) is a leukocyte-restricted adhesion G protein-coupled receptor. Aberrant expression of EMR2 and its highly homologous molecule CD97 have been reported in various human cancers. Herein, we investigate the expression of EMR2 in neoplastic breast human tissue and its relationship with patient survival. EMR2 expression in normal and neoplastic breast tissue was assessed by immunohistochemistry in sections from 10 normal controls and micro-arrayed tissue cores from 69 cases of ductal carcinoma in situ (DCIS) and 272 invasive carcinomas. The pattern and intensity of staining was correlated with the clinicopathological characteristics of each case and the disease outcome. While absent in normal breast epithelium, EMR2 was significantly up-regulated in the cytoplasmic and nuclear compartments of both DCIS and invasive carcinoma, with invasive samples displaying significantly higher expression levels compared with in situ disease. In invasive disease, EMR2 cytoplasmic expression was significantly associated with higher tumour grade but not with patient age, nodal status, tumour size, estrogen receptor expression, relapse-free or overall survival. In contrast, EMR2 nuclear expression correlated negatively with higher tumour grade. Of note, EMR2 nuclear expression was associated with longer relapse-free survival as well as overall survival. This study indicates that EMR2 is expressed in neoplastic breast epithelium and suggests that expression patterns of EMR2 are relevant in breast cancer progression. The association of improved patient survival with higher nuclear expression levels identifies EMR2 as a potential biomarker in patients with invasive breast cancer.

摘要

表皮生长因子样模块包含粘蛋白样激素受体 2(EMR2)是一种白细胞受限的黏附 G 蛋白偶联受体。在各种人类癌症中,已经报道了 EMR2 和其高度同源分子 CD97 的异常表达。在此,我们研究了 EMR2 在肿瘤性乳腺人类组织中的表达及其与患者生存的关系。通过免疫组织化学方法评估了 10 例正常对照组织切片和 69 例导管原位癌(DCIS)和 272 例浸润性癌组织微阵列组织芯中 EMR2 的表达。染色的模式和强度与每个病例的临床病理特征和疾病结局相关。虽然在正常乳腺上皮中不存在,但 EMR2 在 DCIS 和浸润性癌的细胞质和核区均显著上调,浸润性样本的表达水平明显高于原位疾病。在浸润性疾病中,EMR2 细胞质表达与较高的肿瘤分级显著相关,但与患者年龄、淋巴结状态、肿瘤大小、雌激素受体表达、无复发生存或总生存无关。相比之下,EMR2 核表达与较高的肿瘤分级呈负相关。值得注意的是,EMR2 核表达与无复发生存以及总生存时间更长相关。本研究表明 EMR2 在肿瘤性乳腺上皮中表达,并表明 EMR2 的表达模式与乳腺癌的进展相关。与改善的患者生存相关的核表达水平较高表明 EMR2 可能成为浸润性乳腺癌患者的潜在生物标志物。

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