Abstract:
Objective: To study the expression and significance of p-Bad, p-Erk and p-Akt in the progression of breast cancer, including normal breast tissue, ductal hyperplasia, slight and moderate atypical hyperplasia, severe atypical hyperplasia and intraductal carcinoma in situ, as well as invasive ductal carcinoma. Methods: The expression of p-Bad112/136, p-ERK, and p-AKT was examined in 131 paraffin-embedded specimens using immunohistochemical staining and in 27 frozen tissues by Western Blotting. The relationship between the expression of the four proteins and clinicopathological factors was analyzed by Chi-square test and t-test. Results: The positive rates for the expression of the four proteins showed a gradual increase in the progression of breast cancer, and there was a significant difference in the positive rates for expression of the four proteins between the severe atypical hyperplasia, intraductal carcinoma in situ and invasive ductal carcinoma (P=0.034, 0.023, 0.001, 0.001). There was also a significant difference in the positive rate of the p-Bad112/136 expression between the common intraductal hyperplasia and invasive ductal carcinoma of the breast (P=0.002, 0.004). No obvious correlation was found between expression of the four proteins and age, clinical stage or tumor size. However, the four proteins had correlations with histological grading (P=0.039, 0.026, 0.038, 0.026 respectively). As histological grade increased, the expression of all four proteins decreased. p-Erk and pAkt protein expression levels were also related to lymph node metastasis of the armpits (P=0.041, 0.016). Western Blotting analysis for content of the four proteins in invaded adjacent tissue showed there was a significant increase in expression of the four proteins in breast cancer tissues compared with the adjacent breast tissues (P=0.002, 0.001, 0.002, 0.003). There was a positive correlation in the protein content between p-Bad112 and p-Erk (P=0.034), and between p-Bad136 and p-Akt (P=0.020). Conclusion: The results strongly suggest that the levels of the four proteins indicate the potential of metastases to some extent and showed that MAPK/Erk and PI3K/Akt signaling cascades play an important role in the progression of breast cancer.