Co-activation of Hedgehog and Wnt signaling pathways is associated with poor outcomes in triple negative breast cancer

Hedgehog (HH) and Wnt pathway activation have been implicated in poor prognosis of breast cancer. Crosstalk between these two pathways has been demonstrated to be important in breast cancer progression, however the association between these two pathways and breast cancer survival rate is unknown. The present study comprised a cohort of 36 patients with triple negative breast cancer (TNBC) to investigate co-activation of HH and canonical Wnt pathway in association to patient outcome. All patients had varying degrees of cytoplasmic sonic HH and glioma-associated oncogene homolog (Gli)-1 staining, which positively correlated with tumor stage. Nuclear β-catenin was additionally correlated to tumor stage. A significant association was observed between nuclear Gli-1 and nuclear β-catenin. Co-activation of HH and Wnt pathways was associated with poorer prognosis in TNBC patients resulting in a greater risk of early recurrence and decreased overall survival rate compared with patients with only one pathway activated. Therefore, the combined activation status of the HH and Wnt pathways may be a useful prognostic marker for TNBC patients at risk for early recurrence.