目的 比较钙离子激活氯离子通道蛋白1(anoctamin 1,ANO1)和表皮生长因子受体(epidermal growth factor receptor,EGFR)蛋白在小鼠不同食管上皮组织病变中的表达,探讨ANO1、EGFR蛋白表达与小鼠食管上皮病变的关系,为早期食管癌变诊断提供参考。方法 应用化学致癌剂4-硝基喹啉-1-氧化物(4NQO)由饮水法建立小鼠食管癌前病变模型,HE染色光镜下比较观察食管正常组织、轻度、中度、重度异型增生组织及癌变组织变化,采用免疫组化法检测小鼠食管不同病变组织中EGFR、ANO1蛋白表达情况。结果 至实验第24周末,共收集小鼠食管正常组织14份、异型增生组织23份(其中轻度异型增生7份、中度异型增生8份、重度异型增生8份)、癌变组织18份。其中ANO1和EGFR蛋白在食管轻度异型增生组织、中度异型增生组织和正常组织中的阳性率分别为0(0/7)、12.50%(1/8)、0(0/14)和14.29%(1/7)、12.50%(1/8)、7.14%(1/14),差异均无统计学意义(P〉0.05);ANO1和EGFR在癌组织中的阳性率分别为55.56%(10/18)和61.11%(11/18),与ANO1和EGFR在异型增生组织(轻度、中度和重度增生组织)中的阳性率17.39%(4/23)和26.09%(6/23)及其正常组织中的阳性率0(0/14)和7.14%(1/14)比较差异有统计学意义(P〈0.05);ANO1和EGFR在重度异型增生组织中的阳性率分别为37.50%(3/8)和50%(4/8),与正常组织比较差异有统计学意义(P〈0.05)。在18份食管癌组织中,ANO1阳性组EGFR阳性率90%(9/10),ANO1阴性组EGFR阴性率75%(6/8),两种蛋白的表达呈正相关(r=0.663,P=0.003)。结论 ANO1、EGFR蛋白在小鼠食管癌组织及重度异型增生上皮组织中存在过表达,且两种蛋白在食管癌组织中的表达呈正相关,提示ANO1和EGFR两者有可能成为食管癌早期诊断的生物学标志物。
Objective To compare the expression levels of ANO1 (anoctamin 1) and EGFR(epidermal growth factor receptor) protein in different esophageal epithelial lesions, and investigate the relationship between the expression of ANO1 and EGFR and the esophageal epithelial lesion in mice, so as to provide a reference for the early diagnosis of esoph- ageal carcinoma. Methods Establish mice esophageal epithelial dysplasia model with 4NQO, contrast esophagus his- topathologic changes examined with HE staining and light microscope in normal tissues, mild hyperplasia, moderate hy- perplasia, severe hyperplasia and cancerous tissues of mice, examine EGFR and ANO1 protein expressions in different e- sophageal lesions tissues of mice by immunohistochemistry, compare the expression levels of ANO1 and EGFR in esopha- gus normal tissues, dysplasia and cancerous tissues. Results At the end of the experiment, collected 14 cases of normal tissues, 23 cases of esophagus hyperplasia tissues(7 cases of mild hyperplasia, 8 cases of moderate hyperplasia, 8 cases of severe hyperplasia), 18 cases of cancerous tissues. ANO1 and EGFR protein positive rates are 0(0/7) and 14.29% (1/ 7), 12.50% (1/8) and 12.50% (1/8), 0(0/14) and 7.14% (1/14) in esophageal mild hyperplasia, moderate hyperpla- sia and normal tissues, there are no significant differences between every two groups respectively(P〉0.05); ANO1 and EGFR protein positive rates are 55.56%(10/18) and 61.11%(11/18) in carcinoma tissues, 17.39%(4/23) and 26.09O/oo (6/23) in hyperplasia tissues (including mild, moderate and severe hyperplasia) , 0(0/14) and 7.14% (1/14) in normal tissue, there are significant differences between every two groups respectively(P〈0.05)% ANO1 and EGFR protein positive rates are 37.50% (3/8) and 50% (4/8) in severe hyperplasia tissues, there are significant differences between severe hyperplasia group and nomal group respectively(P〈0.05). In all 18 cases of cancerous tissues, E