The Expression Patterns And Clinical Significances Of PAkt And PErk1/2 In Early Stage Breast Cancer

Background and ObjectiveAkt and Erk are epidermal growth factor receptor (EGFR) downstream regulators. Phosphorylation of Akt and Erk (pAkt and pErk1/2) confers resistance to chemotherapy and endocrine therapy. The purpose of this study was to determine the clinical significances of pAkt and pErk1/2 in Chinese patients with early stage breast cancer.MethodsSpecimens were obtained from 286 patients from 2001 to 2008 years in China. All patients received adjuvant anthracycline-based associated or not with taxanes chemotherapy. PAkt and pErk1/2 expressions were determined by immunohistochemistry (IHC). The interactions between pAkt, pErk1/2 and clinical characters were assessed by Chi-square tests and Kaplan-Meier methods.ResultsPAkt and pErk1/2 were expressed in 26.2% and 21.3% of patients, respectively. pAkt expression was correlated with activation of pErk1/2 (p＜0.001). There was no correlation between pAkt, pErk1/2 and disease free survival (DFS) and overall survival (OS) of patients. The patients with pAkt-and pErk1/2-tumors had a longer DFS as compared with expression of pAkt or pErk1/2 (p=0.026). In the hierarchical clustering analysis, we found that the overexpression of pAkt was related with a shorter DFS (p=0.039) for the patients treated with anthracycline-based chemotherapy. In the HER2+patients, the expression of pAkt or pErk1/2 can predicted a poor prognosis (p=0.047 and 0.029, respectively).The expression of pErk1/2 was significantly related a shorter DFS for the patients with hormone receptor positive (p=0.005).ConclusionExpression of pAkt may be a bad predictive marker for the efficiency of anthracycline-based adjuvant chemotherapy; the expression of pAkt or pErk1/2 predicted a shorter DFS for the patients with HER2 overexpression; pErk1/2 was a poor prognosis factor for the hormone receptor positive patients.