Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast

Background: Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/beta-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast. Methods: In the current study, we analyzed the expression patterns and relationships between the key Wnt/beta-catenin signaling components- E-cadherin, Slug and GSK3 beta in IDCs of breast. Results: Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3 beta expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3 beta. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001), and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3 beta nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression. Conclusion: The present study for the first time provided the clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3 beta with beta-catenin in implementing EMT in these cells.