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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 expressions of ANO1, EGFR protein and ANO1 and EGFR protein in different esophageal epithelial tissues in mice and to investigate the relationship between ANO1, EGFR protein expression and Mouse esophageal epithelial lesions, provide a reference for the early diagnosis of esophageal cancer. Methods A mouse model of esophageal precancerous lesion was established by drinking water with 4-nitroquinoline-1-oxide (4NQO) as a chemical carcinogen. HE staining was used to observe normal esophageal tissues, mild, moderate and severe dysplasia Proliferative tissues and cancerous tissues. Immunohistochemistry was used to detect the expression of EGFR and ANO1 in different esophageal tissues of mice. Results At the end of the experiment, 14 mice of esophageal normal tissue, 23 dysplastic tissues (7 mild dysplasia, 8 moderate dysplasia and 8 severe dysplasia) and 18 cancerous tissues were collected. The positive rates of ANO1 and EGFR protein in esophageal dysplasia, moderate dysplasia and normal tissue were 0 (0/7), 12.50% (1/8), 0 (0/14) and 14.29 (1/7), 12.50% (1/8) and 7.14% (1/14), respectively, with no significant difference (P> 0.05). The positive rates of ANO1 and EGFR in cancer tissues were 55.56% 10/18) and 61.11% (11/18) respectively. The positive rates of ANO1 and EGFR in dysplasia tissues (mild, moderate and severe hyperplastic) were 17.39% (4/23) and 26.09% (6/23) ) And its normal tissues (P <0.05). The positive rates of ANO1 and EGFR in severe dysplasia were 37.50 % (3/8) and 50% (4/8), respectively. There were significant differences between the two groups (P <0.05). In 18 esophageal cancer tissues, the positive rate of EGFR was 90% (9/10) in ANO1 positive group and 75% (6/8) in ANO1 negative group, and there was a positive correlation between the two proteins (r = 0.663, P = 0.003). Conclusion ANO1 and EGFR proteins are overexpressed in esophageal cancer tissues and severe dysplasia epithelial tissues, and the expressions of both proteins in esophageal cancer tissues are positively correlated, suggesting that both ANO1 and EGFR may be the early diagnosis of esophageal cancer Biological markers.