LAUSR

BACKGROUND Phyllodes tumors (PT) are rare epithelial-mesenchymal tumors of the breast with malignant potential. Here, we evaluate the nuclear expression of Lymphoid Enhancer Binding Factor 1 (LEF-1), a transcription factor downstream of Wnt/β-catenin signaling, in fibroepithelial lesions of the breast. METHODS Excised fibroepithelial lesions of the breast were retrospectively reviewed, blinded to the original diagnosis, and classified according to WHO criteria. A tissue microarray (TMA) was composed with two representative cores from each case, including 24 benign lesions, 11 borderline phyllodes and 8 malignant phyllodes tumors. β-catenin, LEF-1, p120 and E-cadherin immunohistochemistry (IHC) was performed on the TMA and staining was quantified. RESULTS The malignant/borderline PTs showed higher stromal LEF-1 expression than benign tumors (P<0.001). Stromal cells expressed LEF-1 in 100% (16/16 of core TMA) of malignant phyllodes, compared to 73% (16/22) borderline and 27% (13/48) benign tumors. The average LEF-1 H-score was 24.9, 6.1, and 1.5 for malignant, borderline, and benign tumors, respectively. Nuclear expression of β-catenin in the stromal component was more often seen in malignant than in borderline and benign tumors (44% versus 32% and 23%). Nine TMA cores of malignant tumors without nuclear β-catenin staining demonstrated LEF-1 expression. CONCLUSION Both LEF-1 and nuclear β-catenin showed expression in the majority of borderline/malignant PTs suggesting a biological progression of Wnt/β-catenin pathway activation in the stromal component from benign to malignant tumors. Inhibitors for the Wnt/β-catenin pathway may provide alternative treatment options in the future for malignant or metastatic PTs.