• Paula Blandina Ola Chiappini, Ivan Ucella Dantas de Medeiros, Luiz Guilherme Cenaglia Lima, Jose Humberto Fregnani, Suely Nonogaki, Wilson Luiz da Costa, Felipe Jose Fernandez Coimbra, Milton Jose de Barros E Silva, Celso Abdon Lopes de Mello, Clovis Antonio Lopes Pinto, and Maria Dirlei Begnami.
• AC Camargo Cancer Center, São Paulo, Brazil.
• Arch Med Sci. 2017 Oct 1; 13 (6): 1262-1268.

IntroductionActivation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays a critical role in carcinogenesis and resistance to anticancer drugs. In this study, gastric carcinomas (GC) were investigated and statistical analyses were performed concerning the correlation between the clinicopathological features and activation of the PI3K/AKT pathway.Material And MethodsImmunohistochemistry for p-AKT, p-mTOR and PTEN was performed in 239 GC and 200 non-neoplastic gastric tissues. The clinicopathological parameters were recorded from the medical charts. Statistical significance was defined by a p-value < 0.05.ResultsHigh p-AKT expression was observed in 10% of the normal gastric tissue and in 90% of GC, and it was significantly associated with tumor size (p < 0.001), T3/T4 tumors (p < 0.001), and presence of metastases (p = 0.02). Similarly, p-mTOR positivity was found in GC cells, but not in the normal gastric mucosa, and was correlated with perineural invasion (p = 0.02) and T3/T4 tumors (p = 0.03). On the other hand, PTEN expression was weak and focal in the tumor cells, while in the normal gastric tissue this staining was strong and diffuse. Importantly, the expression of p-mTOR and PTEN was associated with overall survival.ConclusionsThe results of the present study, characterized by the loss of PTEN expression and higher expression of p-AKT and p-mTOR in the majority of tumor cells, apparently are implicated in the carcinogenesis and progression of GC. The identification of p-mTOR and PTEN expression as prognostic factors corroborates the identification and use of potential target drugs that could be more efficient for the treatment of these patients.

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