Epidermal growth factor receptor in non-small-cell lung carcinomas:: Correlation between gene copy number and protein expression and impact on prognosis
Epidermal growth factor receptor in non-small-cell lung carcinomas:: Correlation between gene copy number and protein expression and impact on prognosis
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DOI：
10.1200/jco.2003.11.069
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发表时间：
2003-10-15
影响因子：
45.3
通讯作者：
Franklin, WA
中科院分区：
文献类型：
--
作者：
Hirsch, FR;Varella-Garcia, M;Franklin, WA
目的：表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)中经常过表达，EGFR抑制剂有望成为新的治疗药物。材料和方法：对183例非小细胞肺癌微阵列肿瘤组织中EGFR基因拷贝数和蛋白状态进行了研究，其中鳞癌89例，非鳞癌94例。免疫组织化学方法检测蛋白表达，评分范围为0~400(阳性细胞百分比x染色强度)。结果：EGFR蛋白在62%的非小细胞肺癌中过度表达(25%在201~300分；37%在301~400分)，鳞癌高于非鳞癌(82%vs44%；P<；0001)，80%的细支气管肺泡癌中EGFR蛋白过表达。常见的FISH模式是EGFR基因和7号染色体的平衡二体(40%)和三体(38%)，13%的患者出现平衡多倍体，9%的患者出现基因扩增。基因拷贝数与蛋白表达呈正相关(r=0.4，P<0.01)。结论：EGFR过度表达在非小细胞肺癌中较为常见，在鳞癌中最为突出，且与每细胞基因拷贝数的增加有关。每个细胞的基因拷贝数越高，预后越差。评估EGFR基因和EGFR蛋白的状态和信号蛋白的表达对于正确解释未来使用EGFR抑制剂的临床试验将是重要的。(C)2003年，由美国临床肿瘤学会提供。
Purpose: The epidermal growth factor receptor (EGFR) is frequently overexpressed in non-small-cell lung carcinoma (NSCLC), and EGFR inhibitors are promising new therapeutic agents. The molecular mechanisms responsible for EGFR overexpression are poorly understood.Materials and Methods: Gene copy number and protein status of EGFR were investigated in microarrayed tumors from 183 NSCLC patients, including squamous cell carcinoma (SCC; 89 patients) and non-SCC (94 patients) histologies. Protein expression was assessed by immunohistochemistry on a scale from 0 to 400 (percentage of positive cells x staining intensity). Gene and chromosome 7 copy numbers were identified by fluorescent in situ hybridization (FISH).Results: EGFR protein overexpression was observed in 62% of the NSCLC (25% scored 201 to 300; 37% scored 301 to 400), more frequently in SCC than non-SCC (82% v 44%; P < .001), and in 80% of the bronchioloalveolar carcinomas. The prevalent FISH patterns were balanced disomy (40%) and trisomy (38%) for EGFR gene and chromosome 7 (40%), whereas balanced polysomy was seen in 13% and gene amplification was seen in 9% of the patients. Gene copy number correlated with protein expression (r = 0.4; P < .001). EGFR overexpression or high gene copy numbers had no significant influence on prognosis.Conclusion: EGFR overexpression is frequent in NSCLC, is most prominent in SCC, and correlates with increased gene copy number per cell. High gene copy numbers per cell showed a trend toward poor prognosis. It will be important to evaluate EGFR gene and EGFR protein status and signal protein expression to properly interpret future clinical trials using EGFR inhibitors. (C) 2003 by American Society of Clinical Oncology.