Epidermal growth factor receptor gene amplification in surgical resected Japanese lung cancer
Epidermal growth factor receptor gene amplification in surgical resected Japanese lung cancer
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DOI：
10.1016/j.lungcan.2008.10.005
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发表时间：
2009-06-01
期刊：
影响因子：
5.3
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
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作者：
Sasaki, Hidefumi;Shimizu, Shigeki;Fujii, Yoshitaka
为了评价表皮生长因子受体(EGFR)蛋白表达和拷贝数增加对非小细胞肺癌(NSCLC)患者临床预后的预测作用，我们进行了荧光原位杂交(FISH)和免疫组织化学(IHC)检测。我们研究了109例手术治疗的非小细胞肺癌患者ECFR基因拷贝数增加和EGFR蛋白表达状态。通过基因分型分析和序列分析，分析了有无EGFR突变，并已有报道。EGFR增加的拷贝数定义为Capputio等人。标准。361109例(33.0%)肺癌FISH阳性，其中30例为高度多倍体，6例为基因扩增。FISH阳性病例与预后不良显著相关(对数等级检验p=0.0097)。在EGFR突变患者(n=55)中，FISH阳性病例也与预后不良相关(p=0.0255)。FISH阴性的肿瘤通常是分化较好的组织学类型。吸烟状况(从不吸烟者与吸烟者，p=0.1510)和性别(p=0.5248)与鱼类阳性无关。EGFR IHC结果与FISH结果相关(p=0.004)，但与预后无关(p=0.2815)。尽管表皮生长因子受体FISH阳性率与表皮生长因子受体突变无关(p=0.1973)，但表皮生长因子受体多倍体或扩增与表皮生长因子受体突变相关(p=0.0023)。总之，日本NSCLC患者的EGFR FISH阳性率与西方人群相似，不同于东亚人EGFR突变的较高频率。在非小细胞肺癌中，EGFR基因拷贝数越高，生存期越短。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
To evaluate the epidermal growth factor receptor (EGFR) protein expression and increased copy number as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC), we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the ECFR increased copy number and EGFR protein expression statuses in 109 surgically treated NSCLC cases. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR increased copy number was defined as Cappuzzo et al. criteria. FISH positive was found from 361109 (33.0%) lung cancer patients, including 30 high polysomy cases and 6 gene amplification cases. FISH-positive cases were significantly Correlated with worse prognosis (log-rank test p = 0.0097). Within EGFR-mutant patients (n = 55), FISH-positive cases were also correlated with poor prognosis (p = 0.0255). FISH-negative tumors were found to be more frequently well-differentiated histology. Smoking status (never smoker vs. smoker, p=0.1510), and gender (p=0.5248) did not correlated with FISH positive. EGFR IHC results were correlated with FISH results (p = 0.004), but not correlated with prognosis (p=0.2815). Although EGFR FISH-positive rate did not correlated with EGFR mutation (p = 0.1973), EGFR polysomy or amplification cases were correlated with EGFR mutations (p = 0.0023). In conclusion, the EGFR FISH-positive rate in Japanese patients with NSCLC was similar to rates in Western populations, unlike the higher frequencies of EGFR mutation in East Asians. A high EGFR gene copy number might have shorter survival in NSCLC. (C) 2008 Elsevier Ireland Ltd. All rights reserved.