Expressions of p-AKT (Thr308) and p-AKT (Ser473) proteins in gastrointestinal stromal tumors and their clinicopathological significance and the impact on prognosis

Objective: To investigate the clinicopathological significance of the expressions of phospho-protein kinase B (p-AKT) (Thr308) and p-AKT (Ser473) proteins in gastrointestinal stromal tumor (GIST) tissues and their impact on prognosis. Methods: Tumor samples and clinicopathological data from 102 patients with primary GIST after R0 resection were obtained. Immunohistochemical (IHC) analysis was performed based on tissue microarray (TMA) to estimate the expression pattern of p-AKT (Thr308) and p-AKT (Ser473) in tumor cells. The relationships of these two p-AKT protein expressions with clinicopathological characteristics and relapse-free survival (RFS) were also analyzed. Results: The positive expression rates of p-AKT (Thr308) and p-AKT (Ser473) proteins in GIST tissues were 54.9% and 56.9%, respectively, which were both higher than those in the adjacent normal gastrointestinal stromal tissues (P < 0.05). The expression pattern of p-AKT (Thr308) was associated with tumor size, mitotic index, National Institute of Health (NIH) risk classification and 5-year RFS (P < 0.05), while p-AKT (Ser473) expression was associated with primary tumor site, tumor size, mitotic index, tumor cellularity, necrosis, NIH risk classification and 5-year RFS (P < 0.05). Univariate and multivariate survival analyses demonstrated that the 5-year RFS rate in the GIST patients whose p-AKT (Thr308) and p-AKT (Ser473) were both positively expressed was lower than that in the GIST patients whose p-AKT (Thr308) and p-AKT (Ser473) were both negatively expressed (P < 0.05). Conclusion: The expression of totally activated AKT proteins may be correlated with the occurrence, development and poor prognosis of GIST. The evaluation of co-expression pattern of p-AKT (Thr308) and p-AKT (Ser473) proteins may help predict the prognosis of GIST patients. DOI:10.3781/j.issn.1000-7431.2014.06.010