SFRP2和β-catenin在大肠癌中的表达及其临床意义

Expression of SFRP2 and β-catenin in the carcinogenesisand progression of colorectal carcinoma

目的:探讨分泌型Frizzled相关蛋白2(Secreted Frizzled-related proteins2,SFRP2)和β-连接素(β-catenin)在大肠癌发生、发展中的作用.方法:采用免疫组化SP法检测20例正常大肠黏膜、20例非腺瘤性息肉、36例大肠腺瘤和42例大肠癌组织中的SFRP2和β-catenin蛋白的表达情况,分析二者表达的差异及其与临床病理参数的关系.结果:大肠癌和大肠腺瘤组SFRP2的阳性表达率显著低于正常大肠黏膜和非腺瘤性息肉组(28.57%vs100.0%,95.0%;36.11%vs100.0%,95.0%,均P<0.05);大肠癌中β-catenin膜表达缺失率显著高于正常大肠黏膜、非腺瘤性息肉及大肠腺瘤组(52.4%vs0%,0%,11.1%,均P<0.05);大肠癌和大肠腺瘤组β-catenin异位表达率显著高于正常大肠黏膜和非腺瘤性息肉组(64.3%vs0%,0%;30.6%vs0%,0%,均P<0.05),大肠癌β-catenin异位表达率高于大肠腺瘤(P<0.05);SFRP2表达、β-catenin膜表达缺失及异位表达与大肠癌患者的肿瘤部位、大体形态、肿瘤直径、淋巴转移和Dukes分期无明显关系,而与大肠癌的分化程度密切相关,其中SFRP2表达还与大肠癌的浸润深度密切相关;SFRP2表达与β-catenin膜表达缺失、异位表达均呈明显负相关(r=-0.452,P=0.003;r=-0.519,P=0.000),而β-catenin膜表达缺失与异位表达呈明显正相关(r=0.782,P=0.000).结论:SFRP2和β-catenin的表达与大肠癌的发生、发展密切相关,可能是大肠癌发生的早期事件,且SFRP2表达与β-catenin膜表达缺失、异位表达均呈负相关,前者起抑癌作用,后者起促癌作用.

AIM： To investigate the role of Secreted Frizzledrelated proteins 2 （SFRP2） and β-catenin in carcinogenesis and progression of colorectal carcinoma. METHODS： Expression of SFRP2 and β-catenin proteins were examined immunohistochemically in 20 cases of normal colorectal mucosa, 20 cases of colorectal polyp, 36 cases of colorectal adenomas and 42 cases of colorectal carcinoma. The corresponding clinical data between the expression of SFRP2 and β-catenin proteins were analyzed retrospectively. RESULTS： The positive expression rates of SFRP2 were significantly lower in colorectal carcinoma and colorectal adenoma than in normal colorectal mucosa and colorectal polyp （28.57% vs 100.0%, 95.0%; 36.11% vs 100.0%, 95.0%, all P 〈 0.05）. The reduced membranous β-catenin expression rate was significantly higher in colorectal carcinoma than in normal colorectal mucosa, colorectal polyp and colorectal adenoma （52.4% vs 0%, 0%, 11.1%, all P 〈 0.05）. The cytoplasmic and nuclear β-catenin expression rates were significantly higher in colorectal carcinoma and colorectal adenomas than in normal colorectal mucosa and colorectal polyp （64.3% vs 0%, 0%; 30.6% vs 0%, 0%, all P 〈 0.05）, higher in colorectal carcinoma than in colorectal adenomas （P 〈 0.05）. The positive expression of SFRP2, reduced membranous β-catenin expression and cytoplasmic and nuclear β-catenin expression in colorectal carcinoma were significantly correlated with the tumor differentiation, but not with the tumor position, morphology or size, lymph node metastasis or Duke＇s stage. Besides, the positive expression of SFRP2 was significantly correlated with the depth of invasion in colorectal carcinoma. The positive expression of SFRP2 was negatively correlated with the reduced membranous β-catenin expression （r = -0.452, P = 0.003） and cytoplasmic and nuclear β-catenin expression （r = -0.519, P = 0.000）. There existed positive correlation between the reduced membranous β-catenin expression and cytoplasmic and nuclear β-catenin expression （r = 0.782, P= 0.000）. CONCLUSION： The expression of SFRP2 and β-catenin are closely correlated with the carcinogenesis and progression of colorectal carcinoma, and may be an early event. The positive expression of SFRP2 is negatively correlated with the reduced membranous β-catenin expression and cytoplasmic and nuclear β-catenin expression. The former may inhibit carcinogenesis and latter may promote carcinogenesis.