Prognostic significance of epithelial–mesenchymal transition proteins Twist and Foxc2 in phyllodes tumours of the breast

Abstract

Epithelial-mesenchymal transition (EMT), an important process during embryonic development, is reportedly exploited during tumour progression. Deregulation of EMT-related molecules has been shown in many malignancies, including breast carcinoma. We aim to investigate the clinical relevance and prognostic significance of EMT proteins, Twist and Foxc2, in breast phyllodes tumours (PTs). The study cohort comprised 271 PTs diagnosed from 2003 to 2010. Of these, 188 (69.4%) were benign, 60 (22.1%) borderline, and 23 (8.5%) malignant. Immunohistochemistry for Twist and Foxc2 was performed on tissue microarray sections. Percentage of tumour cells stained was evaluated and correlated with clinicopathological parameters and clinical outcome. Twist and Foxc2 stromal nuclear expression was associated with tumour grade (P=0.038 and 0.012). Foxc2 stromal nuclear expression was positively correlated with epithelial expression (P<0.001), tumour relapse, and metastasis (P=0.037). Furthermore, stromal nuclear immunoreactivity of Twist and Foxc2 was interrelated (P<0.001). Tumours expressing Foxc2 and those co-expressing both Twist and Foxc2 revealed a shorter time to recurrence (P<0.001 and 0.001) and death (P=0.044 and 0.015). Twist and Foxc2 stromal expression in PTs was significantly correlated with tumour grade and worse histological features. In addition, expression of Foxc2 and co-expression of Twist and Foxc2 in the stroma of PTs contributed to poorer prognosis. Clinical relevance of EMT-related molecules may be worthy of further investigation in PTs.