Expression of Phospho-Akt and PTEN Proteins in Human Breast Cancer in Relation to Tumor Progression and Patient Survival

Phosphatidylinositol 3-kinase (PI3-kinase) controls mitogenesis, cellular growth and transformation in a variety of cancers. The serine-threonine kinase Akt is a downstream target of PI3-kinase, and phosphorylated Akt (Phospho-Akt) inhibits apoptosis. Phosphatase and tensin homolog detected on chromosome ten (PTEN) is a tumor suppressor that antagonizes PI3-kinase activity, negatively regulates its downstream-target, Akt, inhibits phosphorylation of Akt, and medicates cell-cycle arrest and apoptosis. To clarify whether the PI3-kinase/Akt pathway and PTEN relate to breast cancer, we examined the expression of pathway-related proteins such as Phospho-Akt and PTEN in clinical specimens. Immunohistochemical analysis was performed on tissue specimens surgically obtained from 221 patients with breast cancer. The association of Phospho-Akt and PTEN expression with clinicopathological variables and the prognosis of patients were analyzed. Of 221 breast carcinomas, positive Phospho-Akt expression was observed in 91 (41.1%) and positive PTEN expression in 119 (53.8%). Phospho-Akt expression and loss of PTEN expression significantly correlated with tumor staging, tumor size and lymph node metastasis. Patients with Phospho-Akt-positive tumors had significantly inferior disease-free survival or over-all survival to those with Phospho-Akt-negative tumors, while those with PTEN positive tumors were better than those with PTEN negative tumors. Moreover, patients with Phospho-Akt-positive and PTEN-negative tumors had a significantly inferior disease-free survival and over-all survival compared to those with Phospho-Akt-negative and PTEN-positive tumors. Multivariate analysis revealed that expression of Phospho-Akt and tumor size were the independent factors (P = 0.024). We demonstrated that the expression of Phospho-Akt significantly correlated with tumor progression and patients survival with breast cancer. Phospho-Akt/PTEN expression status is possibly a definitive prognostic factor in clinical breast cancer.