Proteins from the Wnt pathway are involved in the pathogenesis and progression of mammary phyllodes tumours

Background: The Wnt pathway is important in cell signalling transduction and is involved in the pathogenesis of multiple tumour types. A comprehensive analysis of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours (PTs) has not been previously performed. Aims: To evaluate the immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome. Methods: 65 PTs (34 benign, 23 borderline and 8 malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemical stains were performed on tissue microarrays for beta-catenin, Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately. Results: Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant progressive increases in expression with increasing grade (p = 0.002 and p = 0.02 respectively). Epithelial membranous and stromal nuclear b-catenin, epithelial cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression with increasing tumour grade, however, the differences were not significant. Disease-free survival was significantly decreased (p = 0.0017) with positive epithelial E-cadherin staining. Conclusions: Results suggest that alterations in the Wnt pathway are important in the progression and in the epithelial and stromal interactions in PTs. They have important implications for understanding the pathogenesis of these uncommon but clinically important tumours.