The Hedgehog signaling pathway is associated with poor prognosis in breast cancer patients with the CD44+/CD24- phenotype

Cancer stem cells (CSCs) have been suggested to serve an important role in tumor recurrence and metastasis in breast cancer. The hedgehog (Hh) signaling pathway is essential for the maintenance of breast CSCs. The present study used immunohistochemistry to investigate the expression of Patched (PTCH) and Gli1, which are the main components of the Hh signaling pathway, as well as the expression of cluster of differentiation (CD)44/CD24, which are markers for breast CSCs, in 266 patients with breast cancer. The combined expression of PTCH and Glil was significantly associated with larger tumors (>2.0 cm; P=0.001), lymph node metastasis (P=0.003), invasive lobular carcinoma (P=0.016) and Grade II-III tumors (P<0.001). In addition, PTCH and Glil expression was associated with lymph node metastasis (P=0.005 and P=0.001) and Grade II-II tumors (P=0.020 and P=0.033) in breast cancer patients with the CD44(+)/CD24(-) phenotype. The expression of PTCH and Glil was also associated with significantly shorter overall survival and disease-free survival (DFS) in breast cancer patients with the CD44(+)/CD24(-) phenotype. Multivariate Cox regression analysis demonstrated that PTCH expression and the CD44(+)/CD24(-) phenotype were independent prognostic factors for decreased DFS in patients with breast cancer. These findings suggest that the Hh signaling pathway in breast CSCs may contribute to the poor outcome of patients with breast cancer.