Association of epidermal growth factor receptor (EGFR) gene copy number amplification with neck lymph node metastasis in areca-associated oral carcinomas
Association of epidermal growth factor receptor (EGFR) gene copy number amplification with neck lymph node metastasis in areca-associated oral carcinomas
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DOI：
10.1016/j.oraloncology.2007.02.008
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发表时间：
2008-03-01
期刊：
影响因子：
4.8
通讯作者：
Chang, Kuo-Wei
中科院分区：
文献类型：
--
作者：
Chiang, Wei-Fan;Liu, Shyun-Yeu;Chang, Kuo-Wei
表皮生长因子受体（EGFR）在细胞增殖、分化和转化中发挥重要作用。已经在肿瘤中发现了 EGFR 的几种改变和激活。损害 EGFR 活性的抑制剂已被鉴定并研究用于癌症治疗，因此本研究旨在全面评估槟榔相关口腔鳞状细胞癌（OSCC）中 EGFR 的扩增、突变和表达，这可能有益于靶向治疗。在 33% (14/42) 的 OSCC 病例中发现了 EGFR 基因拷贝数扩增。 6例OSCC具有高拷贝数扩增。对20例OSCC代表性病例的PCR产物直接测序显示EGFR激酶结构域没有体细胞突变。 67% (28/42) 的 OSCC 病例具有细胞核和/或细胞质 EGFR 免疫反应性。与长期咀嚼槟榔的受试者相比，或与匹配的邻近口腔粘膜相比，OSCC 受试者的 EGFR 拷贝数和 EGFR 免疫反应性显着增加（分别为 P < 0.0001 和 P = 0.029）。有趣的是，有淋巴结受累的 OSCC 的 EGFR 基因拷贝数显着高于无淋巴结受累的 OSCC（3.194 +/- 0.740 对比 1.733 +/- 0.246；P = 0.050）。我们的数据表明，基因组扩增可能是槟榔相关 OSCC 中 EGFR 通路激活的遗传基础。 (c) 2008 Elsevier Ltd. 保留所有权利。
Epidermal growth factor receptor (EGFR) has an important role in cell proliferation, differentiation, and transformation. Several alterations and activation of EGFR have been identified in tumors. Inhibitors that impair EGFR activity have been identified and studied for cancer therapy, so the present study was conducted to comprehensively assess the amplification, mutation, and expression of EGFR in areca-associated oral squamous cell carcinoma (OSCC), which might be beneficial for targeting therapy. Gene copy number amplifications of EGFR were identified in 33% (14/42) cases of OSCC. Six cases of OSCC had a high copy number amplification. Direct sequencing of PCR products of 20 representative cases of OSCC revealed no somatic mutation in the kinase domains of EGFR. Sixty-seven percent (28/42) of the OSCC cases had nuclear and/or cytosolic EGFR immunoreactivity. Significant increases in EGFR copy number and EGFR immunoreactivity were found in OSCC subjects compared with long-term areca chewers, or compared with match adjacent oral mucosa (P < 0.0001 and P= 0.029, respectively). Interestingly, OSCC with nodal involvement had significantly higher EGFR gene copy number than OSCC without nodal involvement (3.194 +/- 0.740 versus 1.733 +/- 0.246; P = 0.050). Our data suggest that genomic amplification could be a genetic basis underlying activation of the EGFR pathway in areca-associated OSCC. (c) 2008 Elsevier Ltd. All rights reserved.