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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) in squamous cell carcinoma of the oropharynx by automated qua nlitative analysis (AQUA) and evaluate its value in predicting prognosis . Methods AQUA system was used to analyze the expression of EGFR in a tissue microarray composed of 95 cases of oropharyngeal carcinoma paraffin specimens. The correlation between clinical and histopathological data was analyzed. Cytokeratin was used as a marker. The images automatically displayed by the digital camera showing the intensity of their expression were loaded into an automated analysis system to set the tumor range for each microarray spot while the target antigen EGFR was visualized with a conjugated antibody to the fluorogenic pro-Cy5 and the EGFR expression was automatically calculated Pixel density, digitizing its expression, produces a digitally continuous variable that is proportional to the number of target antigens that are positively expressed per unit area. According to the median of expression variables, the expression level was divided into high and low expression groups. Results ① The local recurrence rate at 5 years was 57.8% in EGFR cells in high expression group and 17.2% in low expression group (P <0.01). In the high expression of EGFR nuclear cell in tumor tissue The 5-year local recurrence rate was 54.4% in the low-expression group and 21.4% in the low-expression group (P <0.05). ②The 5-year tumor-free survival rate was significantly higher in the EGFR tumor cells (19.0% (19.0%) were also significantly different from those in low-expression group (43.4%) and low-expression group (44.8%) (all P <0.05). ③Multivariate risk regression analysis, Tumor cells and nuclear EGFR overexpression are an independent prognostic negative correlation factor, with statistical significance. Conclusion The AQUA system can effectively analyze the expression of EGFR in paraffin sections and reveal the relationship between the expression of EGFR and the biological effects of EGFR. The AQUA value of EGFR is expected to become a target of predicting the sensitivity of targeted therapy to EGFR Learning indicators.