[Activation and prognostic significance of AKT, NF-kappaB and STAT3 in breast cancer with lymph node metastasis and estrogen receptor expression].

BACKGROUND OBJECTIVE: Being downstream targets of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) and epidermal growth factor receptor (EGFR) pathways, serine/threonine kinase AKT, nuclear factor-кB (NF-кB) and signal transducer and activator of transcription-3 (STAT3), play important roles in cell proliferation, apoptosis and oncogenesis. This study was to investigate the activation and prognostic values of AKT, NF-кB and STAT3 in breast cancer with lymph node metastasis and estrogen receptor (ER) expression. METHODS: The expression of phosphatized AKT (p-AKT), NF-кB (p-NF-кB) and STAT3 (p-STAT3), and the expression of EGFR, PTEN, HER-2, and Ki67 in tissue samples from 130 breast cancer patients with lymph node metastasis and ER expression were detected by immunohistochemistry. RESULTS: The activity of AKT (p-AKT) and NF-кB (p-NF-кB) were correlated to HER-2 overexpression (P=0.023 and P=0.017) and histological grade of breast cancer (P=0.035 and P=0.004). The expression of p-AKT, p-NF-кB and p-STAT3 had no correlation to tumor size, EGFR overexpression, and proliferation index assessed by Ki67. The expression of p-AKT was positively correlated to that of p-NF-кB (r=0.43, P0.001) and negatively correlated to that of p-PTEN (r=-0.20, P=0.002). The overexpression of p-AKT and p-NF-кB were significantly related to shorter survival (P=0.002 and P=0.003). The up-regulation of p-NF-кB expression was also related to enhanced risk of recurrence and metastasis (P=0.006). Cox multivariate analysis showed that the expression of p-AKT and p-NF-кB were correlated to shorter overall survival (OS) (P=0.017 and P=0.008) and disease-free survival (DFS) (P=0.005 and P=0.012), while the expression of p-STAT3 had no correlation to OS (P=0.332) and DFS (P=0.237). CONCLUSIONS: The activation of AKT and NF-кB, but not STAT3, significantly contributes to the progression of breast cancer. Activated AKT and NF-кB may indicate poor prognosis of breast cancer with lymph node metastasis and ER expression.