He Yanjiao, Liu Zhaoxia, Qiao Chao, Xu Miaosheng, Yu Jin, Li Guang
Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
Mol Med Rep. 2014 Jan;9(1):137-43. doi: 10.3892/mmr.2013.1774. Epub 2013 Nov 4.
The aim of this study was to investigate the expression of β-catenin, axin, cyclin D1 and c-myc, and their correlation with various clinicopathological factors of breast carcinoma. Using immunohistochemistry, the expression of axin, β-catenin, cyclin D1 and c-myc proteins was detected in 168 breast carcinomas and 40 normal breast tissue samples, as well as in 72 breast intraductal proliferative lesions. Correlations among the expression of these proteins with the clinicopathological factors of breast carcinomas were subsequently analyzed. Gene mutations of β-catenin (exon 3) in 44 cases of breast carcinoma were analyzed using polymerase chain reaction (PCR) followed by direct sequencing. In normal tissue, the epithelial cells demonstrated a marked membranous expression of β-catenin protein at cell-cell boundaries and positive axin expression; cyclin D1 and c-myc expression, however, were negative. The abnormal rate of β-catenin expression and the overexpression of cyclin D1 and c-myc were higher in breast carcinomas compared with breast cystic hyperplasia tissues. Positive axin expression levels were lower in breast carcinomas compared with breast intraductal proliferative lesions and normal breast tissues. Axin expression correlated inversely with tumor size, histological grade, clinical tumor, node, metastasis (TNM) stage and lymph node metastasis. The abnormal expression of β-catenin and the overexpression of cyclin D1 were correlated, and the overexpression of c-myc was correlated with tumor size, histological grade, clinical TNM stage and lymph node metastasis. The abnormal expression of β-catenin was correlated with the overexpression of cyclin D1, but not with the overexpression of c-myc. Lower levels of axin expression were correlated with higher levels of nuclear β-catenin expression. Mutations in the β-catenin gene were not detected in 44 cases of breast carcinoma. The abnormal expression of β-catenin may be key in the carcinogenesis and progression of human breast carcinoma by upregulating the expression of cyclin D1. The abnormal expression of β-catenin, the reduced expression of axin, and the overexpression of cyclin D1 and c-myc may be useful markers for determining metastasis, providing a prognosis for human breast carcinoma and for guiding treatment.
本研究旨在探讨β-连环蛋白、轴抑制蛋白、细胞周期蛋白D1和c-myc的表达及其与乳腺癌各种临床病理因素的相关性。采用免疫组织化学方法，检测168例乳腺癌、40例正常乳腺组织样本以及72例乳腺导管内增生性病变中轴抑制蛋白、β-连环蛋白、细胞周期蛋白D1和c-myc蛋白的表达。随后分析这些蛋白表达与乳腺癌临床病理因素之间的相关性。采用聚合酶链反应（PCR）及直接测序法分析44例乳腺癌中β-连环蛋白（第3外显子）的基因突变情况。在正常组织中，上皮细胞在细胞-细胞边界处显示出明显的β-连环蛋白膜性表达以及轴抑制蛋白阳性表达；然而，细胞周期蛋白D1和c-myc表达为阴性。与乳腺囊性增生组织相比，乳腺癌中β-连环蛋白表达异常率以及细胞周期蛋白D1和c-myc的过表达更高。与乳腺导管内增生性病变和正常乳腺组织相比，乳腺癌中轴抑制蛋白阳性表达水平更低。轴抑制蛋白表达与肿瘤大小、组织学分级、临床肿瘤、淋巴结、转移（TNM）分期及淋巴结转移呈负相关。β-连环蛋白的异常表达与细胞周期蛋白D1的过表达相关，c-myc的过表达与肿瘤大小、组织学分级、临床TNM分期及淋巴结转移相关。β-连环蛋白的异常表达与细胞周期蛋白D1的过表达相关，但与c-myc的过表达无关。轴抑制蛋白表达水平较低与核β-连环蛋白表达水平较高相关。44例乳腺癌中未检测到β-连环蛋白基因突变。β-连环蛋白的异常表达可能通过上调细胞周期蛋白D1的表达在人类乳腺癌的发生和发展中起关键作用。β-连环蛋白的异常表达、轴抑制蛋白表达降低以及细胞周期蛋白D1和c-myc过度表达可能是判断转移、为人类乳腺癌提供预后及指导治疗的有用标志物。
