Immunohistochemical expression of homeoproteins Six1 and Pax3 in breast phyllodes tumours correlates with histological grade and clinical outcome

Abstract

Homeoproteins are transcription factors which critically regulate developmental processes. Deregulated expression of homeoproteins is observed in several malignancies, such as breast cancer and rhabdomyosarcoma, and contributes to malignant progression. We aimed to investigate the expression and prognostic importance of Six1 and Pax3 homeoproteins in phyllodes tumours - a group of uncommon biphasic tumours comprising both epithelial and stromal components. A total of 272 cases diagnosed from January 2003 to December 2010 were included in this study - 189 (69.5%) benign, 60 (22.1%) borderline and 23 (8.4%) malignant tumours. Immunohistochemistry was performed on tissue microarray sections using antibodies against Six1 and Pax3. Staining H-score was assessed in epithelium and stroma separately, and correlated with tumour grade, clinicopathological parameters and prognosis. Tumour grade was associated positively with stromal cytoplasmic expression (P<0.001; P=0.011) but correlated negatively with epithelial nuclear expression (P=0.013; P=0.007) of both Six1 and Pax3. High stromal cytoplasmic expression of Six1 was associated with metastasis (P=0.044) and shorter time to recurrence (P=0.056). Pax3 stromal cytoplasmic expression was associated with poorer overall survival (P=0.033). Six1 and Pax3 expression is correlated with tumour grade, unfavourable clinicopathological parameters and poorer clinical outcome, suggesting that both proteins may play a role in malignant progression.