ORIGINAL ARTICLES

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

R Z Karim^1,2,3, S K Gerega⁴, Y H Yang^4,5, L Horvath^6,7, A Spillane⁸, H Carmalt⁹, R A Scolyer^1,2,3, C S Lee^1,3,10,11,12

¹ Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
² Cancer Institute NSW, Sydney, NSW, Australia
³ Discipline of Pathology, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia
⁴ Sydney Bioinformatics, The University of Sydney, Sydney, NSW, Australia
⁵ School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, Australia
⁶ Sydney Cancer Centre, Sydney, NSW, Australia
⁷ Garvan Institute, Sydney, NSW, Australia
⁸ Discipline of Surgery, Faculty of Medicine, The University of Sydney, Sydney, NSW, Australia
⁹ Visiting Breast Surgeon, Royal Prince Alfred Hospital, Sydney, NSW, Australia
¹⁰ Department of Anatomical Pathology, Liverpool Hospital, Sydney, NSW, Australia
¹¹ Discipline of Pathology, School of Medicine, The University of Western Sydney, Sydney, NSW, Australia
¹² Cancer Pathology, Bosch Institute, The University of Sydney, Sydney, NSW, Australia

Correspondence to:
^{Correspondence to} Dr R Z Karim, Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Sydney, Australia; rooshdiya.karim{at}email.cs.nsw.gov.au

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 β-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 β-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.

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