Expression and significance of Wnt signaling components and their target genes in breast carcinoma

The aim of this study was to investigate the expression of -catenin, axin, cyclin D1 and c-myc, and their correlation with various clinicopathological factors of breast carcinoma. Using immunohistochemistry, the expression of axin, -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 -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 -catenin protein at cell-cell boundaries and positive axin expression; cyclin D1 and c-myc expression, however, were negative. The abnormal rate of -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 -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 -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 -catenin expression. Mutations in the -catenin gene were not detected in 44 cases of breast carcinoma. The abnormal expression of -catenin may be key in the carcinogenesis and progression of human breast carcinoma by upregulating the expression of cyclin D1. The abnormal expression of -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.