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


METHODS
The expression of phosphatized AKT (p-AKT), NF-kappaB (p-NF-kappaB) 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-kappaB (p-NF-kappaB) 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-kappaB 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-kappaB (r=0.43, P<0.001) and negatively correlated to that of p-PTEN (r=-0.20, P=0.002). The overexpression of p-AKT and p-NF-kappaB were significantly related to shorter survival (P=0.002 and P=0.003). The up-regulation of p-NF-kappaB 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-kappaB 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-kappaB, but not STAT3, significantly contributes to the progression of breast cancer. Activated AKT and NF-kappaB may indicate poor prognosis of breast cancer with lymph node metastasis and ER expression.
Liu
Cong
C
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
Zhou
Sheng
S
Ke
Chang-Shu
CS
Li
Na-Ping
NP
Wu
Ren-Liang
RL
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010766:Phosphorylation; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015996:Survival Rate
D016328:NF-kappa B; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase