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

Abstract

Estradiol exerts most of its effects by direct binding to the estrogen receptor in breast carcinoma, ERβ expression is a useful biomarker for breast cancer in a manner that is independent of ERa expression. However, studies evaluating ERβ 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 ERa, ERβ, HER-2/neu and AKT staining with the presence of metastases or survival. Immunohistochemical staining was employed to determine the expression of ERa, ERβ, pAkt and HER-2/neu in 110 cases of primary breast carcinoma. Positive ERa, ERβ, 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 ERa, ERβ, p53 (P >0.05) expressions. Survival analysis showed that pAkt positivity was associated with poor disease-free survival of the patients. 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 ERa and ERβ-independent mechanisms in breast cancer.