Wnt Signaling Pathway in Invasive Ductal Carcinoma of the Breast: Relationship between β-Catenin, Disheveled and Cyclin D1 Expression

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Abstract
Objective: The Wnt/β-catenin signaling cascade is an important signal transduction pathway in human cancers. Overexpression of β-catenin and its downstream effector, cyclin D1, is implicated in malignant transformation and acquisition of an invasive tumor phenotype. This study aimed to determine the clinical significance of Wnt/β-catenin canonical pathway components in breast cancer. Methods: Expression of β-catenin, disheveled (Dvl) and cyclin D1 was examined in invasive ductal carcinomas (IDCs) of the breast by immunohistochemical analysis. Results: Of the 98 IDCs analyzed, 30% of tumors displayed both nuclear and cytoplasmic staining of Dvl protein, while 52% showed nuclear localization. Loss of cell surface β-catenin was observed in 66% of breast carcinomas, whereas nuclear expression was observed in 48% IDCs. Cyclin D1 overexpression was observed in 60% IDCs; 31/59 (53%) of these tumors showed nuclear expression of β-catenin, suggesting upregulation of the canonical Wnt/β-catenin pathway. Our study demonstrates a significant association between nuclear localization of Dvl and β-catenin (p < 0.01, OR = 15.8). Conclusion: To our knowledge, this is the first study showing an association between nuclear localization of Dvl and β-catenin in IDCs and suggests the upregulation of Wnt/β-catenin pathway components, β-catenin, Dvl and cyclin D1 in IDCs of the breast.