Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression.

OBJECTIVE

The Wnt/beta-catenin signaling cascade is an important signal transduction pathway in human cancers. Overexpression of beta-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/beta-catenin canonical pathway components in breast cancer.

METHODS

Expression of beta-catenin, dishevelled (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 beta-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 beta-catenin, suggesting upregulation of the canonical Wnt/beta-catenin pathway. Our study demonstrates a significant association between nuclear localization of Dvl and beta-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 beta-catenin in IDCs and suggests the upregulation of Wnt/beta-catenin pathway components, beta-catenin, Dvl and cyclin D1 in IDCs of the breast.