β-catenin/Wnt signalling pathway in fibromatosis, metaplastic carcinomas and phyllodes tumours of the breast

• Published in: Modern pathology 2010-11, Vol.23 (11), p.1438-1448
• Main Authors: Lacroix-Triki, Magali, Geyer, Felipe C, Lambros, Maryou B, Savage, Kay, Ellis, Ian O, Lee, Andrew HS, Reis-Filho, Jorge S
• Format: Article
• Language: English
• Subjects: 631/80/86; 692/699/67/1347; beta Catenin - analysis; beta Catenin - genetics; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Breast Neoplasms - chemistry; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Carcinoma - chemistry; Carcinoma - genetics; Carcinoma - pathology; Cell Nucleus - chemistry; Diagnosis, Differential; DNA Mutational Analysis; England; Female; Fibroma - chemistry; Fibroma - genetics; Fibroma - pathology; France; Humans; Immunohistochemistry; Laboratory Medicine; Medicine; Medicine & Public Health; Metaplasia; Mutation; original-article; Pathology; Phyllodes Tumor - chemistry; Phyllodes Tumor - genetics; Phyllodes Tumor - pathology; Predictive Value of Tests; Signal Transduction - genetics; Wnt Proteins - analysis
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/modpathol.2010.141

Wnt signalling pathway is known to have a critical role in carcinogenesis and in epithelial-to-mesenchymal transition. Upon Wnt activation, β -catenin is translocated from the membrane to the cytoplasm and nucleus, where it interacts with transcriptional activators. It has been suggested that various spindle cell lesions of the breast may harbour Wnt pathway activation. Given that β -catenin nuclear localization constitutes a good surrogate 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. A total of 52 metaplastic breast carcinomas, eight fibromatoses and 23 phyllodes tumours were retrieved from our institutions’ archives. We performed immunohistochemistry using two anti- β -catenin antibodies. In all, three fibromatoses and 21 metaplastic breast carcinomas were subjected to CTNNB1 ( β -catenin encoding gene) mutation analysis by direct gene sequencing. A good correlation between the two antibodies was observed (Spearman's r >0.82, P S/P and 41T>T/A were found in samples of fibromatosis. In conclusion, β -catenin nuclear expression is a common feature in fibromatoses and in the stromal component of phyllodes tumours, but may also be observed in metaplastic breast carcinomas. β -catenin nuclear expression should not be used as a single marker to differentiate fibromatosis from other spindle cell tumours of the breast.