Beta-Catenin/WNT Signaling Pathway in Fibromatosis, Metaplastic Carcinomas and Phyllodes Tumours of the Breast
FC Geyer, M Lacroix-Triki, K Savage, AH Lee, JS Reis-Filho. ICR, London, United Kingdom; Institut Claudius Regaud, Toulouse, France; Nottingham City Hospital, Nottingham, United Kingdom
Background: Wnt signalling pathway is known to play a critical role in carcinogenesis and in epithelial to mesenchymal transition. Upon Wnt activation, β-catenin (CTNNB1) is translocated from the membrane to the cytoplasm and nucleus, where it interacts with transcriptional activators. It has been demonstrated that fibromatoses harbour APC mutations and that metaplastic breast carcinomas may harbour CTNNB1 mutations, both leading to Wnt pathway activation. Given that β-catenin nuclear localisation constitutes a good marker of Wnt canonical pathway activation, we have investigated the distribution of β-catenin in spindle cell lesions of the breast and whether it could be employed in the differential diagnosis of these lesions.
Design: 52 metaplastic breast carcinomas (MBCs) (22 spindle cell carcinomas, 17 carcinomas with squamous metaplasia, 13 carcinomas with heterologous elements), eight fibromatosis and 23 phyllodes tumours (PTs), were retrieved from our institutions' archives. We performed immunohistochemistry using two commercially available anti-β-catenin antibodies on whole tissue sections. β-catenin nuclear, membranous and cytoplasmic expression was assessed in each tumour component using the Allred scoring system. Each component of a case with a score>2 was considered as positive.
Results: A good correlation between the 2 antibodies used in this study was observed (Spearman's rho 0.675, p<0.001). All fibromatoses analysed expressed nuclear β-catenin. 23% of MBCs displayed β-catenin nuclear expression. No association between the subtype of MBC and β-catenin nuclear expression was found. Membranous expression was lower in spindle cell carcinomas (mean score 4) than in carcinomas with squamous metaplasia and with heterologous elements (mean scores 8 and 7, respectively). In PTs, β-catenin nuclear staining was observed in both the epithelial and spindle cell components. Spindle cells of benign and malignant PTs displayed nuclear β-catenin expression in 94% and 57% of cases, respectively. Membranous expression was observed only in the epithelial component of all PTs.
Conclusions: β-catenin nuclear expression is a common feature in fibromatosis and in the stromal component of PTs, but may also be observed in MBCs. β-catenin nuclear expression should not be used as a single marker to differentiate fibromatosis from other spindle cell tumours of the breast.
Monday, March 22, 2010 1:00 PM
Poster Session II # 50, Monday Afternoon