Division of Surgical Oncology, Department of Surgery, University of Louisville, 315 E. Broadway, Louisville, KY 40202, USA.
J Gastrointest Surg. 2012 May;16(5):946-55. doi: 10.1007/s11605-011-1778-1. Epub 2011 Nov 17.
There has been recent widespread enthusiasm in epidermal growth factor (EGFR) as a molecularly active target in esophageal adenocarcinoma (EAC). However, there is limited data on the extent of EGFR expression in EAC. Thus, the aim of this study was to evaluated EGFR, pErk1/2, and total Erk1/2 expression in malignant and benign specimens.
Baseline expression of EGFR in the human normal squamous, Barrett's, and EAC cell lines were determined as well as after bile acid treatment and curcumin pretreatment. In addition, EGFR expression was also evaluated in 60 matched normal and malignant EAC resected specimens.
The in vitro studies in the Het-1a, BarT, and OE19 cell lines failed to show any measurable expression of EGFR via Western blot technique. The marker serving as the positive control for the study, MnSOD, showed expression in each cell line for all three treatment regimens at approximately 24 kDa EGFR, showing moderate staining in the malignant tumor specimens and low staining in the benign tissue specimens. pErk1/2 showed low staining in the malignant tumor specimens and no staining in the benign tissue specimens. Total Erk1/2 showed high staining in both the malignant tumor specimens and benign tissue specimens. The differences in the mean staining scores for the malignant versus benign tissue specimens for pErk1/2 and total Erk1/2 are not statistically significant (p = 0.0726 and p = 0.7054, respectively).
Thus, in conclusion, EGFR expression has been confirmed to be limited to non-existent in EAC and thus its use as a clinically active target is limited at best. Prior to the use of these expensive anti-EGFR therapies, confirmation of overexpression should be verified.
表皮生长因子(EGF)作为食管腺癌(EAC)的一种分子活性靶点,近来受到广泛关注。然而,关于 EAC 中 EGFR 表达的程度,数据有限。因此,本研究旨在评估恶性和良性标本中 EGFR、pErk1/2 和总 Erk1/2 的表达。
测定人正常鳞状、巴雷特和 EAC 细胞系中 EGFR 的基础表达,以及胆汁酸处理和姜黄素预处理后。此外,还评估了 60 对匹配的 EAC 切除恶性和良性标本中 EGFR 的表达。
体外研究在 Het-1a、BarT 和 OE19 细胞系中,Western blot 技术未能检测到 EGFR 的可测量表达。作为研究阳性对照的标志物 MnSOD,在每种细胞系的三种处理方案中均有表达,约为 24 kDa EGFR,在恶性肿瘤标本中表现为中度染色,在良性组织标本中表现为低度染色。pErk1/2 在恶性肿瘤标本中染色较低,在良性组织标本中无染色。总 Erk1/2 在恶性肿瘤标本和良性组织标本中均表现为高染色。pErk1/2 和总 Erk1/2 的恶性与良性组织标本平均染色评分之间的差异无统计学意义(p=0.0726 和 p=0.7054)。
因此,总之,EGFR 表达已被证实局限于不存在于 EAC 中,因此其作为临床活性靶点的应用是有限的。在使用这些昂贵的抗 EGFR 治疗之前,应验证过表达的确认。