表皮生长因子受体及Ⅲ型突变体在食管癌的表达及意义

摘要

背景与目的:已有研究显示表皮生长因子受体(epidermal growth factor receptor,EGFR)及Ⅲ型突变体(epidermal growth factor receptor variant Ⅲ,EGFRvⅢ)在一系列恶性肿瘤的发生发展中起重要作用,但EGFR、EGFRvⅢ与食管癌的关系目前尚未明确.本研究探讨EGFR及EGFRvⅢ与食管癌组织发生发展的关系.方法:应用免疫组织化学及蛋白印迹实验(Western Blot)检测66例人食管癌组织及癌旁正常组织EGFR及EGFRvⅢ表达,评价EGFR及EGFRvⅢ在食管癌患者的性别,年龄、TNM分期及病理分级等临床参数组的表达分布.Pearson相关性检验分析EGFR及EGFRvⅢ表达相关性.结果:免疫组化显示EGFR、EGFRvⅢ在肿瘤组织表达的平均灰度净值分别为25.4±3.2、22.5±4.2,在癌旁正常食管组织平均灰度净值分别为5.0±3.5、5.5±3.0,肿瘤组织与正常组织相比差异均有显著性(P<0.000).Western Blot显示EGFR、EGFRvⅢ在肿瘤组织表达的平均灰度诤值分别为1.37±0.41、0.83±0.15,在瘤旁正常食管组织平均灰度净值分别为0.21±0.09、0.08±0.05,肿瘤组织与正常组织相比差异均有显著性(P<0.05).在性别、年龄、肿瘤大小和生长方式方面EGFR、EGFRvⅢ的表达分布差异均无显著性(P >0.05),而在TNM分期、病理分级和淋巴结转移方面两者差异均有显著性(P<0.05).免疫组化检测两蛋白表达净灰度值相关系数r为0.701(P<0.0001),Western Blot检测两种蛋白表达相关系数r为0.556(P=0.031).两种研究方法均提示EGFR与EWRvⅢ在食管癌中的表达成较好线性正相关性. 结论:EGFRvⅢ在食管癌特异性表达,EGFR与EGFRvⅢ在食管癌中的表达呈线性正相关,提示EGFR与EGFRvⅢ与食管癌发生、发展密切相关.%Background and purpose: It has been reported that epidermal growth factor receptor (EGFR) and epidermal growth factor receptor variant Ⅲ (EGFRv Ⅲ) play important roles in the progression of various cancers. This research was to detect the expression and relation of EGFR and epidermal growth factor receptor variant Ⅲ (EGFRv Ⅲ) to human esophageal carcinoma. Methods: In 66 human esophageal carcinoma tissues, the expression of EGFR and EGFRv Ⅲ were detected by imrnunohistochemistry and western-blot. The expression of EGFR and EGFRv Ⅲ along with the patients' clinicopathologic factors was retrospectively analyzed. Correlation analysis between EGFRv Ⅲ and EGFR was analyzed by Pearson correlation coefficient. Results: The average gray scale values of EGFR in esophageal carcinoma and normal tissues by immunohistochemistry were 25.4±3.2 and 5.0±3.5, which showed a significant difference (t=5.574, P=0.000). And the average gray scale values of EGFRv Ⅲ in esophageal carcinoma and normal tissues were 22.5±4.2 and 5.5±3.0, which also showed a significant difference (t=6.701,P=0.000). The average gray scale values of EGFR in esophageal carcinoma and normal tissues respectively by western-blot were 1.37±0.41 and 0.21±0.09, which showed a significant difference (t=10.704, P=0.000) And the average gray scale values of EGFRv Ⅲ respectively were 0.828±0.15 and 0.083±0.049, which had a significant difference (t=9.362, P=0.000). Significant differences were observed in TNM-stage, lymphatic metastasis and tumor classification in both the expression of EGFR (P<0.05) and EGFRv Ⅲ (P<0.05), and but there were no obvious differences in gender, age, minor size, growth pattern in both the expression of EGFR (P<0.05) and EGFRvⅢ (P<0.05). Correlation analysis showed that there was strong association of the expression between EGFR and EGFRv Ⅲ both detected by immunohistochemistry (r=0.701,P<0.0001) and western-blot respectively(r=0.556, P=0.031). Conclusion: Our data suggests that EGFRvⅢ is over-expressed in human esophageal carcinoma. Combination of EGFR and EGFRvⅢ could be useful markers for tumorgenesis and differentiation of human esophageal carcinoma.