AKT signaling pathway in invasive ductal carcinoma of the breast: correlation with ERα, ERβ and HER-2 expression

Aims and background. Estradiol exerts most of its effects by direct binding to the estrogen receptor in breast carcinoma, ER beta expression is a useful biomarker for breast cancer in a manner that is independent of ER alpha expression. However, studies evaluating ER beta expression with certain tumor variables, such as tumor grade and disease-free survival, had produced conflicting results. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. The current study attempted to compare the relative associations of variables including ER alpha, ER beta, HER-2/neu and AKT staining with the presence of metastases or survival. Methods and study design. Immunohistochemical staining was employed to determine the expression of ER alpha, ER beta, pAkt and HER-2/neu in 110 cases of primary breast carcinoma. Results. Positive ER alpha, ER beta, pAkt and HER-2/neu expressions were respectively observed in 46.4% (51/110), 59.1% (65/110), 40.9% (45/110) and 31.8% (35/110) of the tumors. pAkt was significantly associated with HER-2/neu overexpression (P < 0.005) and axillary lymph node metastasis (P < 0.05). However, there was no significant relationship between pAkt and ER alpha, ER beta, p53 (P > 0.05) expressions. Survival analysis showed that pAkt positivity was associated with poor disease-free survival of the patients. Conclusions. The current study suggested that activity of the Akt signaling pathway may indicate a poor prognosis in patients with breast carcinoma. The results implied that estrogen can activate the PI3K-Akt pathway through ER alpha and ER beta-independent mechanisms in breast cancer.