摘要
目的评价自动定量分析法(automated qua nlitative analysis,AQUA)测定表皮生长因子受体(epidermaI growth factor receptor,EGFR)在口咽部鳞状细胞癌组织中的表达水平,了解其在判定预后中的价值。方法AQUA系统分析了一个由95例口咽癌石蜡标本组成的组织微阵列中EGFR的表达,并进行临床和组织病理学资料的相关性分析,将细胞角蛋白(cytokeratin)设为标志物,将数码相机自动拍摄的显示其表达强度的图像载入自动分析系统,设定了每个微阵列点的肿瘤范围,同时用荧光色素原Cy5的耦连抗体显示靶抗原EGFR,并自动计算EGFR表达的像素密度,将其表达数字化,这样就产生了一个数字化的连续变量,它与单位面积内阳性表达的靶抗原分子数量成正比。按表达变量的中位数划分其表达强弱,分成高、低表达组。结果①5年局部复发率,肿瘤组织中EGFR细胞高表达组为57.8％,而低表达组为17.2％,相比有显著的统计学意义(P＜0.01)；在肿瘤组织中EGFR细胞核高表达组的5年局部复发率为54.4％,低表达组为21.4％,相比也有统计学意义(P＜0.05)；②在5年无瘤生存率方面,EGFR肿瘤细胞高表达组(19.0％)及细胞核高表达组(19.0％),分别与细胞低表达组(43.4％)和细胞核低表达组(44.8％)相比也有显著的统计学差异(P均＜0.05)：③多变量风险回归分析,肿瘤细胞和细胞核EGFR高表达都是一个独立的预后负相关因子,有统计学意义。结论AQUA系统可以有效地对石蜡组织切片中EGFR的表达进行连续变量分析,揭示了EGFR的表达与其产生的生物学作用的联系,EGFR的AQUA数值有望成为能预测EGFR靶向治疗敏感性的一个生物学指标。
OBJECTIVE To evaluate the expression of epidermal growth factor receptor（EGFR） as a molecular target for oropharyngeal squamous cell carcinomas measured by automated quantitative analysis（AQUA） and its significance of EGFR expression, especially nuclear EGFR expression in the prognosis of cancer. METHODS The EGFR protein expression was measured by AQUA on a tissue microarray composed of 95 oropharyngeal cancer specimens. The relationship between the quantitative expression of EGFR and clinical, pathological data were analyzed. Automated quantitative analysis used cytokeratin to define pixels as cancer （tumor area） within the array spot and measured intensity of EGFR expression using a Cy5 conjugated antibody within the tumor area. A continuous score was generated, which was directly proportional to the number of molecules per unit area, and cases were defined as high expressors if their scores were above the median expression level. RESULTS Patients with high tumor EGFR expression levels had a local recurrence rate of 57.8 % compared with 17.2% for patients with low tumor EGFR expression （P〈0.01）. Similarly, patients with high nuclear EGFR expression had a local recurrence rate of 54.4 % compared with 21.4% for patients with low nuclear EGFR expression （P〈0.05）. Additionally, patients with high tumor and nuclear EGFR expression levels had lower disease-free survival rates compared with that in patients with low tumor and nuclear EGFR levels （19.0 % versus 43.4 % and 19.0 % versus 44.8 %, respectively. P〈0.05 for each）. In multivariable analysis adjusting for well-characterized prognostic variables, high tumor and nuclear EGFR expression levels retained their prognostic significance. CONCLUSION The AQUA system provides a continuous measurement of EGFR on paraffin-embedded tissue and is able to reveal the association between EGFR expression and outcome expected by the biological role of EGFR. In the future, EGFR AQUA score may be useful in predicting response to EGFR-targeted therapy.
出处
《中国耳鼻咽喉头颈外科》
北大核心
2006年第8期533-538,共6页
Chinese Archives of Otolaryngology-Head and Neck Surgery
基金
美国耶鲁大学OHSE基金(1334715)
美国耶鲁大学医学研究启动基金(0410027126)
Doris Duke慈善基金会
Virginia Alden Wright基金
关键词
受体
表皮生长因子
口咽肿瘤
数值分析
计算机辅助
荧光免疫测定
受体
胞质和核
Receptor, Epidermal Growth Factor
Oropharyngeal Neoplasms
Numerical Analysis,Computer-Assisted
Fluoroimmunoassay
Receptors,Cytoplasmic and Nuclear
