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黑色素瘤中的表皮生长因子受体:临床意义及潜在治疗靶点

EGFR in melanoma: clinical significance and potential therapeutic target.

作者信息

Boone Barbara, Jacobs Koen, Ferdinande Liesbeth, Taildeman Jasmien, Lambert Jo, Peeters Marc, Bracke Marc, Pauwels Patrick, Brochez Lieve

机构信息

Department of Dermatology, University Hospital Ghent, Ghent, Belgium.

出版信息

J Cutan Pathol. 2011 Jun;38(6):492-502. doi: 10.1111/j.1600-0560.2011.01673.x. Epub 2011 Feb 24.

DOI:10.1111/j.1600-0560.2011.01673.x
PMID:21352258
Abstract

BACKGROUND

The role of epidermal growth factor receptor (EGFR) has been established in a range of neoplasms. In melanoma, data on EGFR protein expression are conflicting. Fluorescence in situ hybridization (FISH) analysis for EGFR gene expression in melanoma showed EGFR gene amplification to be linked with worse prognosis. Cetuximab has been shown to suppress the formation of metastasis in mice.

METHODS

EGFR protein expression and gene copy number status were evaluated by means of immunohistochemistry and FISH in melanoma samples of patients with known clinicopathological data. Associations between EGFR expression and prognostic parameters were investigated. The effect of different cetuximab concentrations on the BLM melanoma cell line was evaluated by means of methyl tetrazolium (MTT), sulforhodamine B (SRB) and Matrigel invasion assays.

RESULTS

EGFR protein expression was more frequently observed in patients with a positive sentinel lymph node. However, EGFR immunostaining has no predictive value. The presence of EGFR polysomy was associated with thicker tumors. Treatment of the BLM melanoma cell line with different concentrations of cetuximab reduced the invasive capacity of the cells, but did not alter cell viability or growth.

CONCLUSION

EGFR appears to be involved in progression and metastasis of a subset of melanomas. Targeting EGFR could therefore represent a therapeutic option for these melanomas.

摘要

背景

表皮生长因子受体(EGFR)在一系列肿瘤中的作用已得到证实。在黑色素瘤中,关于EGFR蛋白表达的数据存在矛盾。黑色素瘤中EGFR基因表达的荧光原位杂交(FISH)分析显示EGFR基因扩增与较差的预后相关。西妥昔单抗已被证明可抑制小鼠转移的形成。

方法

采用免疫组织化学和FISH方法对具有已知临床病理数据的黑色素瘤患者样本中的EGFR蛋白表达和基因拷贝数状态进行评估。研究EGFR表达与预后参数之间的关联。通过甲基噻唑基四唑(MTT)、磺基罗丹明B(SRB)和基质胶侵袭试验评估不同浓度西妥昔单抗对BLM黑色素瘤细胞系的影响。

结果

前哨淋巴结阳性的患者中更常观察到EGFR蛋白表达。然而,EGFR免疫染色没有预测价值。EGFR多体性的存在与较厚的肿瘤相关。用不同浓度的西妥昔单抗处理BLM黑色素瘤细胞系可降低细胞的侵袭能力,但不改变细胞活力或生长。

结论

EGFR似乎参与了一部分黑色素瘤的进展和转移。因此,靶向EGFR可能是这些黑色素瘤的一种治疗选择。

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