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表皮生长因子受体表达与墨西哥胃癌患者的不良生存相关:使用标准化免疫组织化学检测系统的多变量分析

Epidermal growth factor receptor expression correlates with poor survival in gastric adenocarcinoma from Mexican patients: a multivariate analysis using a standardized immunohistochemical detection system.

作者信息

Gamboa-Dominguez Armando, Dominguez-Fonseca Claudia, Quintanilla-Martinez Leticia, Reyes-Gutierrez Edgardo, Green Dan, Angeles-Angeles Arturo, Busch Raymonde, Hermannstädter Christine, Nährig Jörg, Becker Karl-Friedrich, Becker Ingrid, Höfler Heinz, Fend Falko, Luber Birgit

机构信息

Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.

出版信息

Mod Pathol. 2004 May;17(5):579-87. doi: 10.1038/modpathol.3800085.

Abstract

The aim of the study was to determine epidermal growth factor receptor (EGFR) expression in gastric adenocarcinoma by standardized immunohistochemistry and to correlate EGFR expression with clinical features and patient survival. EGFR expression was investigated in paraffin sections of resection specimens of 89 gastric carcinomas from Mexican Mestizo patients using standardized immunohistochemistry with antigen retrieval (Dako EGFRpharmDx assay detection system). Membrane staining of EGFR was evaluated in the neoplastic cells and graded using a semiquantitative score (0-3+). Of the 89 carcinomas examined, staining of neoplastic cells was weak in 17 (19.1%, score 1+), moderate in 16 (18.0%, score 2+), and strong in nine cases (10.1%, score 3+). EGFR reactivity was heterogeneous, frequently showing completely negative up to 3+ positive areas within an individual tumor. EGFR reactivity score correlated with distant metastases (P=0.002) and clinical stage (P=0.033). EGFR score 0/1+ was significantly associated with an increase in patient survival when compared to score 2+/3+ (P=0.0006). In a multivariate analysis, EGFR positive cells in muscularis or subserosa (P=0.004), distant metastases (P=0.016) and residual disease (P=0.039) were significantly correlated with decreased survival. The prognosis was associated with the EGFR reactivity score (P=0.003), distant metastases (P=0.0001) and residual disease (P=0.012) in a univariate analysis. EGFR reactivity in neoplastic cells is an independent prognostic factor in gastric adenocarcinoma. The relevance of the heterogeneity in EGFR expression with regard to tumor progression, metastasis and anti-EGFR therapy needs to be studied.

摘要

本研究的目的是通过标准化免疫组织化学方法测定胃腺癌中表皮生长因子受体(EGFR)的表达,并将EGFR表达与临床特征及患者生存率相关联。使用标准化免疫组织化学及抗原修复方法(Dako EGFRpharmDx检测系统),对89例来自墨西哥梅斯蒂索患者的胃癌切除标本石蜡切片进行EGFR表达研究。对肿瘤细胞中的EGFR膜染色进行评估,并采用半定量评分(0 - 3+)进行分级。在89例检测的癌组织中,肿瘤细胞染色为弱阳性的有17例(19.1%,评分为1+),中度阳性的有16例(18.0%,评分为2+),强阳性的有9例(10.1%,评分为3+)。EGFR反应性具有异质性,在单个肿瘤内常表现为从完全阴性到3+阳性区域。EGFR反应性评分与远处转移(P = 0.002)及临床分期(P = 0.033)相关。与评分为2+/3+相比,EGFR评分为0/1+与患者生存率增加显著相关(P = 0.0006)。在多变量分析中,肌层或浆膜下层的EGFR阳性细胞(P = 0.004)、远处转移(P = 0.016)及残留病灶(P = 0.039)与生存率降低显著相关。在单变量分析中,预后与EGFR反应性评分(P = 0.003)、远处转移(P = 0.0001)及残留病灶(P = 0.012)相关。肿瘤细胞中的EGFR反应性是胃腺癌的一个独立预后因素。EGFR表达异质性在肿瘤进展、转移及抗EGFR治疗方面的相关性有待研究。

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