EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus
EGFR protein overexpression and gene amplification in squamous cell carcinomas of the esophagus
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DOI：
10.1002/ijc.21454
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发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Ooi, A
中科院分区：
文献类型：
--
作者：
Hanawa, M;Suzuki, S;Ooi, A
在许多癌症中观察到表皮生长因子受体（EGFR）的过度表达，有时还伴有基因扩增。最近，开发了几种针对 EGFR 的临床疗法，但这些疗法的资格标准尚未完全确定。为了制定食管鳞状细胞癌（ESCC）的资格标准，我们试图澄清：（i）EGFR过度表达的确切频率，（ii）蛋白质过度表达与基因扩增之间的关系，（iii）基因扩增与特定基因突变之间的关系以及（iv）EGFR状态与临床或病理特征之间的相关性。免疫组织化学显示，在检查的 106 个 ESCC 中，有 53 个 (50%) EGFR 蛋白过度表达。荧光原位杂交（FISH）显示，53 个肿瘤中有 15 个肿瘤有明显的 EGFR 基因扩增，32 个肿瘤中 EGFR 拷贝数稍高，6 个肿瘤中没有增加。基因扩增与高水平过表达显着相关。 EGFR 外显子 19 和 21 的直接测序显示，15 个表现出基因扩增的肿瘤中没有突变，25 个未表现出基因扩增的肿瘤中没有突变。 EGFR的过表达与肿瘤的侵袭深度显着相关。总之，抗 EGFR 疗法可能适合 ESCC 患者。我们假设免疫组织化学/FISH 联合分析将澄清蛋白质和基因功能的畸变，并有助于识别那些可能受益于抗 EGFR 治疗的患者。 (c) 2005 年 Wiley-Liss, Inc.
Overexpression of epidermal growth factor receptor (EGFR) is observed in many cancers, sometimes accompanied by gene amplification. Recently, several clinical therapies targeting EGFR were developed, but the eligibility criteria for these therapies is not fully established. To develop such eligibility criteria for esophageal squamous cell carcinoma (ESCC), we sought to clarify: (i) the exact frequency of EGFR overexpression, (ii) the relationship between protein overexpression and gene amplification, (iii) the relationship between gene amplification and specific gene mutations and (iv) the correlation between the status of EGFR and clinical or pathological features. Immunohistochemistry revealed that EGFR protein is overexpressed in 53 (50%) of the 106 ESCC examined. Fluorescence in situ hybridization (FISH) indicated clear EGFR gene amplification in 15 of the 53 tumors, somewhat higher EGFR copy in 32 cases, and no increase in 6 cases. Gene amplification was significantly associated with high level overexpression. Direct sequencing of exons 19 and 21 of EGFR revealed no mutations in 15 tumors exhibiting gene amplification, and no mutations in 25 tumors not exhibiting gene amplification. Overexpression of EGFR was significantly correlated with depth of invasion of the tumor. In conclusion, anti-EGFR therapies may be appropriate for patients with ESCC. We assume that combined analyses by immunohistochemistry/FISH would clarify aberrations in protein and gene function, and could help to identify those patients who may benefit from anti-EGFR therapy. (c) 2005 Wiley-Liss, Inc.