Departments of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Clin Cancer Res. 2011 May 1;17(9):2947-54. doi: 10.1158/1078-0432.CCR-10-2040. Epub 2011 Feb 25.
Epidermal growth factor receptor (EGFR) overexpression correlates with recurrence and with treatment resistance in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the relationship of EGFR gene copy number utilizing FISH and protein expression with automated quantitative analysis (AQUA) and to correlate those with patient outcome.
A tissue microarray composed of 102 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis; Abbott Laboratories) and EGFR protein expression using AQUA analysis of EGFR staining scored on a scale of 0 to 255. We evaluated associations of EGFR FISH status and AQUA score with clinicopathologic parameters and survival prognosis.
Eleven (17.2%) of 64 tumors with FISH results showed EGFR high polysomy and/or gene amplification (FISH positive). Protein levels assessed by AQUA in FISH-positive cases were significantly higher (P = 0.04) than in FISH-negative cases. Using the continuous AQUA scores for EGFR expression, AQUA and FISH showed significant agreement (Pearson's ρ = 0.353, P = 0.04). Patients with high tumor EGFR protein expression had inferior 5-year overall survival (27.7%) compared with those with low tumor EGFR expression (54%; P = 0.029). There was no significant association between EGFR FISH status and overall survival (P = 0.201). In the multivariate model, high tumor EGFR protein expression status remained an independent prognostic factor for overall survival (P = 0.047).
EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. EGFR protein levels assessed by AQUA strongly predict for patient outcome in HNSCC, whereas EGFR FISH status does not provide prognostic information.
表皮生长因子受体（EGFR）的过表达与头颈部鳞状细胞癌（HNSCC）的复发和治疗耐药有关。本研究旨在评估利用 FISH 和自动定量分析（AQUA）检测 EGFR 基因拷贝数与蛋白表达的关系，并将其与患者的预后相关联。
构建了一个由 102 例接受（放）化疗的 HNSCC 组成的组织微阵列，并利用 FISH（Vysis；雅培实验室）检测 EGFR 拷贝数，利用 AQUA 分析 EGFR 染色的评分（范围为 0 到 255）来检测 EGFR 蛋白表达。我们评估了 EGFR FISH 状态和 AQUA 评分与临床病理参数和生存预后的相关性。
11 例（17.2%）FISH 结果显示 EGFR 高多倍体和/或基因扩增（FISH 阳性）的肿瘤。FISH 阳性病例的 AQUA 评估的蛋白水平显著升高（P = 0.04）。使用 EGFR 表达的连续 AQUA 评分，AQUA 和 FISH 显示出显著的一致性（Pearson's ρ = 0.353，P = 0.04）。高肿瘤 EGFR 蛋白表达的患者 5 年总生存率（27.7%）明显低于低肿瘤 EGFR 表达的患者（54%；P = 0.029）。EGFR FISH 状态与总生存率之间无显著相关性（P = 0.201）。在多变量模型中，高肿瘤 EGFR 蛋白表达状态仍然是总生存率的独立预后因素（P = 0.047）。
如果对蛋白含量进行定量和自动分析（如通过 AQUA），EGFR 蛋白含量与基因拷贝数相关。通过 AQUA 评估的 EGFR 蛋白水平强烈预测 HNSCC 患者的预后，而 EGFR FISH 状态不能提供预后信息。
