APC、β-catenin、C-myc和Cyclin D1在大肠癌组织中的表达及其意义

背景与目的:Wnt信号转导通路成员各癌基因、抑癌基因的异常,激活下游相关靶基因的转录,在肿瘤发生发展中起重要作用.本研究通过检测不同大肠组织中APC、β-catenin、C-myc和Cyclin D1的表达情况,探讨其在大肠癌发生中的意义.方法:应用免疫组织化学方法检测30例正常大肠粘膜、30例大肠腺瘤、10例大肠腺瘤恶变及50例大肠癌组织中APC、β-catenin、C-myc和Cyclin D1蛋白的表达情况.以β-catenin在细胞膜表达为正常表达,而在胞浆和/或胞核表达为异位表达.结果:大肠癌和大肠腺瘤恶变组织APC阳性率分别为44.0%和40.0%,显著低于大肠腺瘤(86.7%)和正常大肠粘膜(100%)(P＜0.01).大肠癌、大肠腺瘤恶变组织和大肠腺瘤β-catenin胞浆和/或胞核异位表达率分别为62.0%、50.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01),大肠癌β-catenin异位表达率显著高于大肠腺瘤(P＜0.01).大肠癌、大肠腺瘤恶变组织、大肠腺瘤中C-myc表达率分别为56.0%、60.0%、46.7%,均显著高于正常大肠粘膜(0%)(P＜0.01),而Cyclin D1阳性率分别为66.0%、60.0%、30.0%,均显著高于正常大肠粘膜(0%)(P＜0.01).大肠癌Cyclin D1表达率显著高于大肠腺瘤(P＜0.01).大肠癌中β-catenin异位表达与C-myc和Cyclin D1表达呈正相关关系(r=0.63,P＜0.01;r=0.57,P＜0.01),而与APC表达呈负相关关系(r=-0.39,P＜0.05).结论:大肠癌组织中存在APC低表达和/或β-catenin异位表达,以及C-myc和Cyclin D1的过度表达,4种基因蛋白可能在大肠癌发生过程中起重要作用.

Expression and significance of APC, beta-catenin, C-myc, and Cyclin D1 proteins in colorectal carcinoma

BACKGROUND & OBJECTIVE: The abnormal oncogenes and antioncogenes in Wnt signaling transduction pathway activate downstream specific target genes, and may play important roles in tumorigenesis and tumor progression. This study was to examine the expression of adenomatous polyposis coli (APC), beta-catenin, C-myc, and Cyclin D1 in different colorectal tissues, and investigate their possible roles in the carcinogenesis of colorectal carcinoma. METHODS: The expression of APC, beta-catenin, C-myc, and Cyclin D1 in 30 specimens of normal colorectal mucosa, 30 specimens of colorectal adenoma, 10 specimens of colorectal adenoma with malignancy, and 50 specimens of colorectal carcinoma was examined by immunohistochemistry. The expression of beta-catenin on cell membrane was regarded as normal, and its expression in cytoplasm and nuclei was defined as ectopic expression. RESULTS: The positive rate of APC was significantly lower in colorectal carcinoma and colorectal adenoma with malignancy than in colorectal adenoma and normal colorectal mucosa (44.0% and 40.0% vs. 86.7% and 100.0%, P<0.01). The ectopic expression rate of beta-catenin was significantly higher in colorectal carcinoma, colorectal adenoma with malignancy, and colorectal adenoma than in normal colorectal mucosa (62.0%, 50.0%, and 30.0% vs. 0%, P<0.01), and significantly higher in colorectal carcinoma than in colorectal adenoma (P<0.01). The positive rate of C-myc was significantly higher in colorectal carcinoma, colorectal adenoma with malignancy, and colorectal adenoma than in normal colorectal mucosa (56.0%, 60.0%, and 46.7% vs. 0%, P<0.01). The positive rate of Cyclin D1 was significantly higher in colorectal carcinoma, colorectal adenoma with malignancy, and colorectal adenoma than in normal colorectal mucosa (66.0%, 60.0%, and 30.0% vs. 0%,P<0.01), and significantly higher in colorectal carcinoma than in colorectal adenoma (P<0.01). The ectopic expression of beta-catenin was positively correlated to the expression of C-myc and Cyclin D1 (r=0.63,P<0.01; r=0.57, P<0.01), and negatively correlated to the expression of APC (r=-0.39, P<0.05). CONCLUSION: The reduced expression of APC, ectopic expression of beta-catenin, overexpression of C-myc and Cyclin D1 exist in colorectal carcinoma, which may play important roles in the carcinogenesis of colorectal carcinoma.