Significance of Akt Expression in Node-negative Breast Cancer

Han, Hyung Joon; You, Young Dong; Lee, Jae Bok; Son, Gil Soo; Bae, Jung Won; Kim, Ae Ree; Kim, In Sun; Koo, Bum Hwan

Abstract

BACKGROUND
Patients with lymph node-negative breast cancer show a 10-year recurrence rate of approximately 20%. In node-negative breast cancer, the prognostic factors are age, menopause, tumor size, hormone receptors, p53, DNA ploidy, Ki-67 index (Ki-67) and c-erbB2. Of these, ErbB2 (the protein of the c-erbB2 gene) is a member of the receptor tyrosine kinase family. Overexpression of ErbB2 is known to regulate cell proliferation, differentiation, growth and apoptosis via the ErbB2/Phosphoinositol 3-Kinase (PI 3-K)/Akt signaling pathway. Therefore, it is important to identify high- risk patients that would benefit from adjuvant therapies related with ErB2. For this purpose, the prognostic relevance of the ErbB2/PI 3-K/Akt pathway was examined in node-negative breast cancer. METHODS: A retrospective analysis was performed on the hospital records of all 72 patients diagnosed with breast cancer, and who underwent surgical treatment between January 1996 and December 2003. Clinicopathological data were compared with the results of immunohistochemical staining using the phospho-specific antibody for the expression of Akt. RESULTS: The mean age of the patient's was 48.6 years. Phospho-Akt (pAkt) was expressed in 24 cases (33.3%), but there was no statistical relationship between pAkt expression and the known prognostic factors of breast cancer. There was no statistical significance in the survival rates between the pAkt positive and negative expression groups (P=0.123). In the ErbB2 positive patients, the expression of pAkt was associated with a shorter disease-free survival (P=0.045), and the disease-free survival was shorter in patients whose tumors expressed pAkt and had a high level of Ki-67 (P=0.040). CONCLUSION: The co-expression of ErbB2 and pAkt positivity implied a poor prognosis in node-negative breast cancer patients, and the co-expression of high Ki-67 and pAkt positivity also revealed a poor prognosis in these patients. These results show that the expression of pAkt could be considered a prognostic marker of node-negative breast cancer with ErbB2 positive expression and high levels of Ki-67.