大肠癌中APC、β-catenin和cyclinD1的表达及其临床意义

Expression and clinical significance of APC,β-catenin and cyclinD1 proteins in colorectal carcinoma

目的:探讨APC、β-catenin和cyclinD1在大肠癌发生、发展过程中的作用。方法:应用免疫组织化学方法检测30例正常大肠黏膜、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和cyclinD1蛋白的表达情况。结果:大肠癌和大肠腺瘤恶变APC阳性率分别为44.0%,40.0%,显著低于大肠腺瘤(86.7%)和正常大肠黏膜(100%)(P<0.01)。大肠癌、大肠腺瘤恶变和大肠腺瘤β-catenin胞浆和/或胞核异位表达率分别为:62.0%,50.0%,30.0%,显著高于正常大肠黏膜(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)。大肠癌中β-catenin膜表达缺失率为:46.0%,显著高于大肠腺瘤(10.0%)和正常大肠黏膜(0)(P<0.01)。大肠癌、大肠腺瘤恶变、大肠腺瘤cyclinD1阳性率分别为:66.0%,60.0%,30.0%,显著高于正常大肠黏膜(0)(P<0.01),大肠癌cyclinD1阳性率显著高于大肠腺瘤(P<0.01)。β-catenin膜表达缺失和cyclinD1高表达与大肠癌组织分化程度、浸润深度、淋巴结转移、Dukes分期有关。APC蛋白表达与大肠癌组织分化程度有关。大肠癌中β-catenin异位表达与cyclinD1阳性表达呈正相关关系(r=0.57,P<0.01),而与APC阳性表达呈负相关关系(r=-0.39,P<0.05)。结论:APC失表达和/或β-catenin异位表达,可能是原癌基因cyclinD1激活的重要原因,并在大肠癌发生过程中起重要作用,可能是大肠癌发生的早期事件。β-catenin膜表达缺失和cyclinD1高表达与大肠癌的侵袭、转移有关。

Objective：To investigate the role of APC, β -catenin and cyclinD1 in the carcinogenesis and progression of colorectal carcinoma. Methods： Expression of APC, β- catenin and cyclinD1 proteins were examined by immunohistochemistry in 30 cases of normal colorectal mucosa, 30 cases of colorectal adenoma, 10 cases of colorectal adenoma carcinogenesis and 50 cases of colorectal carcinoma. Results： The positive expression rates of APC were 44.0% and 40.0% respectively in colorectal carcinoma and colorectal adenoma carcinogenesis, and both of the rates were significantly lower than that of colorectal adenoma （ 86.7% ） and normal colorectal mucosa（ 100.0% ） （ P 〈0.01 ）. The cytoplasmic and nuclear β- catenin expression rates were 62.0% ,50.0% and 30.0% respectively in colorectal carcinoma, colorectal adenoma carcinogenesis and colorectal adenoma, and all of the rates were significantly higher than that of normal colorectal mucosa（0）（ P 〈 0.01 ）. The cytoplasmic and nuclear β -catenin expression rate in colorectal carcinoma was significantly higher than that of colorectal adenoma（ P 〈 0.01 ）. The reduced membranous β - catenin expression rate in colorectal carcinoma was significantly higher than that of colorectal adenoma and normal colorectal mucosa（ P 〈 0.01 ）. The positive expression rates of cyclinD1 were 30.0% ,60.0% and 66.0% respectively in colorectal carcinoma , colorectal adenoma carcinogenesis and colorectal adenoma , and all of the rates were significantly higher than that of normal colorectal mucosa（0） （P 〈 0.01 ）. The positive expression rate of cyclinD1 in colorectal carcinoma was significantly higher than that of colorectal adenoma（ P 〈 0.01 ）. The reduced membranous β - catenin expression and cyclinD1 overexpression were closely related with the tissue differentiation degree, the depth of invasion, lymph node metastasis and Dukes stage in colorectal carcinoma. The expression of APC was closely related with the tissue differentiation degree in colorectal carcinoma. The cytoplasmic and nuclear β- catenin expression was thus in positive correlation with the expression of cyclinD1 （r = 0. 57 ,P 〈 0.01 ）, and was in negative correlation with the expression of APC （r = -0. 39, P 〈 0.05 ）. Conclusion： The reduced cytoplasmic APC expression , the cytoplasmic and nuclear β - catenin expression may activate the expression of cyclinD1, which play a pivotal role in the carcinogenesis of colorectal carcinoma, and may be an early event . The reduced membranous - catenin expression and cyclinD1 overexpression may be related to the invasion and metastasis of colorectal carcinoma.