NDRG3 protein expression is associated with aggressive biologic phenotype and unfavorable outcome in patients with invasive breast cancer

The N-myc downstream regulated gene (NDRG) protein family consists of 4 members (NDRG1, NDRG2, NDRG3, and NDRG4), that have been reported to be aberrantly expressed in human cancers. Furthermore, NDRG3 protein expression is known to promote tumor angiogenesis and cell growth. The aim of this study was to investigate the clinical significance of NDRG3 expression in invasive breast cancer (IBC). NDRG3 expression was evaluated immunohistochemically in tissue microarrays of 1339 IBC samples, and associations between NDRG3 expression and clinicopathologic parameters, including prognosis, were examined. NDRG3 protein expression was observed in 194 (14.5%) cases, and found to be associated with an age of >= 50 yrs (P=0.043), a high histologic grade (P < 0.001), high Ki-67 index (P < 0.001), negatively for estrogen or progesterone receptor (both P < 0.001), and positive HER2 status (P < 0.001). No significant association was found between NDRG3 expression and tumor size, lymph node status, lymphovascular invasion, or androgen receptor status. NDRG3-positive tumors were found to be associated with poorer overall survival (OS, P=0.035), and multivariate analyses showed NDRG3 expression independently predicted OS (P=0.011) and disease-free survival (P=0.051). This study shows NDRG3 protein expression is a promising prognostic marker in IBC.