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表皮生长因子受体的表达水平与结直肠腺瘤的进展相关:一种表面生物标志物的验证

The level of epidermal growth factor receptors expression is correlated with the advancement of colorectal adenoma: validation of a surface biomarker.

作者信息

Williet Nicolas, Petcu Carmen Adina, Rinaldi Leslie, Cottier Michèle, Del Tedesco Emilie, Clavel Léa, Dumas Olivier, Jarlot Camille, Bouarioua Nadia, Roblin Xavier, Peoc'h Michel, Phelip Jean-Marc

机构信息

Department of Hepato-Gastroenterology, University Hospital of Saint-Etienne, France.

Department of Pathology, University Hospital of Saint-Etienne, France.

出版信息

Oncotarget. 2017 Mar 7;8(10):16507-16517. doi: 10.18632/oncotarget.14961.

Abstract

INTRODUCTION

Data about the expression of Epidermal Growth Factor Receptors (EGFRs) in colorectal adenomas remain scarce.

RESULTS

101 patients were enrolled including 53 controls. All adenomas (n = 38) and CRC (n = 5) were EGFR positive. Hyperplastic polyps (HP) (n = 8) and control colons (n = 53) were EGFR negative in half of cases (p < 0.0001). A well significant gradient of increased EGFR expression was observed between adjacent mucosa, hyperplastic lesions, low grade dysplasia (LGD) (n = 30), high grade dysplasia (HGD) adenomas (n = 9) and cancers (p < 0.0001). EGFR overexpression was reported in 100% of cancers, 77.8% of HGD, and 10% of LGD adenomas. By multivariate analysis in adenomas, associated factors with EGFR overexpression were HGD and tubulo-villous feature.

MATERIALS AND METHODS

All patients undergoing colonoscopy in the university center of Saint-Etienne were eligible to the study from December 2015 to March 2016. In patients with colorectal neoplasia (lesions group), biopsies were performed on the lesion before its resection, and on the adjacent and distal colon mucosa. In control group, biopsies were performed in the right and left side colon. The EGFR expression was assessed by immunohistochemical scores (Goldstein grade, intensity of staining, composite score), using a primary mouse monoclonal antibody (EGFR, clone 113, Novocastra). Outcomes were compared using Kruskal-Wallis and/or Mann-Whitney-U tests, appropriately. The associated clinical, endoscopic and histological factors with EGFR overexpression (composite score ≥ 6) were assessed for adenomas by logistic regression.

CONCLUSIONS

EGFR are early involved in colorectal carcinogenesis, and their expression is strongly correlated to the neoplasia stage, leading to validate EGFR as an interesting surface biomarker of adenomas.

摘要

引言

关于表皮生长因子受体(EGFRs)在大肠腺瘤中表达的数据仍然很少。

结果

共纳入101例患者,其中53例为对照组。所有腺瘤(n = 38)和结直肠癌(n = 5)的EGFR均呈阳性。增生性息肉(HP)(n = 8)和对照结肠(n = 53)在半数病例中EGFR呈阴性(p < 0.0001)。在相邻黏膜、增生性病变、低级别异型增生(LGD)(n = 30)、高级别异型增生(HGD)腺瘤(n = 9)和癌症之间观察到EGFR表达增加的显著梯度(p < 0.0001)。100%的癌症、77.8%的HGD和10%的LGD腺瘤中报告有EGFR过表达。在腺瘤的多因素分析中,与EGFR过表达相关的因素是HGD和管状绒毛特征。

材料与方法

2015年12月至2016年3月期间,在圣艾蒂安大学中心接受结肠镜检查的所有患者均符合本研究条件。在患有结直肠肿瘤的患者(病变组)中,在病变切除前对病变及其相邻和远端结肠黏膜进行活检。在对照组中,在结肠左右侧进行活检。使用小鼠单克隆一抗(EGFR,克隆号113,诺华卡斯达)通过免疫组化评分(戈尔茨坦分级、染色强度、综合评分)评估EGFR表达。适当使用Kruskal-Wallis和/或Mann-Whitney-U检验比较结果。通过逻辑回归评估腺瘤中与EGFR过表达(综合评分≥6)相关的临床、内镜和组织学因素。

结论

EGFR早期参与结直肠癌发生,其表达与肿瘤分期密切相关,从而验证EGFR作为腺瘤一个有意义的表面生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/143b/5369981/b0f9ceb06265/oncotarget-08-16507-g001.jpg

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