Expression of lymphoid enhancer-binding factor 1 in breast fibroepithelial lesions

Phyllodes tumors (PTs) 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/beta-catenin signaling, in fibroepithelial lesions of the breast. Excised fibroepithelial lesions of the breast were retrospectively reviewed, blinded to the original diagnosis, and classified according to World Health Organization (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 PTs. beta-Catenin, LEF-1, p120, and E-cadherin immunohistochemistry was performed on the TMA, and staining was quantified. 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 with 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 beta-catenin in the stromal component was more often seen in malignant than in borderline and benign tumors (44% versus 32% and 23%, respectively). Nine TMA cores of malignant tumors without nuclear beta-catenin staining demonstrated LEF-1 expression. Both LEF-1 and nuclear beta-catenin showed expression in the majority of borderline/malignant PTs suggesting a biological progression of Wnt/beta-catenin pathway activation in the stromal component from benign to malignant tumors. Inhibitors for the Wnt/beta-catenin pathway may provide alternative treatment options in the future for malignant or metastatic PTs. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

The study evaluates the nuclear expression of LEF-1 and beta-catenin in fibroepithelial lesions of the breast, finding significantly increased expression in malignant/borderline Phyllodes. This suggests an important role of the Wnt/beta-catenin signaling pathway in the biological progression of Phyllodes tumors.