Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer

Abstract

Despite the great interest in mammalian target of rapamycin (mTOR) as a potential anticancer therapy target, the prognostic role of mTOR in gastric cancer has not been elucidated. In this study, we investigated mTOR expression in gastric cancer tissues and in metastatic lymph nodes and examined its association with clinical outcome. A total of 290 patients with pT2b gastric cancer were enrolled in this study. Patients were divided into 3 groups according to metastatic lymph node status: Group 1 contained 96 patients without lymph node metastasis, Group 2 contained 102 patients with a few (1-2) metastatic lymph nodes and Group 3 contained 92 patients with extensive (>16) lymph node metastasis. Phosphorylated mTOR expression was determined immunohistochemically using tissue microarrays. p-mTOR expression was observed in 36.5% of the gastric cancer tissues in Group 1, 39.2% in Group 2 and 60.9% in Group 3. A significant correlation was found between p-mTOR expression in gastric cancer tissues and in metastatic lymph nodes. The Borrmann type in Group 1, perineural invasion and p-mTOR expression in metastatic lymph nodes in Group 2 and p-mTOR expression in metastatic lymph nodes in Group 3 were found to be independent prognostic factors of disease-free survival. The 5-year disease free survival rate of Group 2 patients was 84.4% in negative p-mTOR and 66.1% in positive p-mTOR expression in metastatic lymph nodes (p = 0.015). The 5-year disease free survival rate of Group 3 patients was 37.3% in negative p-mTOR and 14.9% in positive p-mTOR expression in metastatic lymph nodes (p = 0.037). There was a linear correlation between the rate of tumor recurrence and mTOR expression scores in metastatic lymph nodes. In pT2b gastric cancer, p-mTOR expression in gastric cancer is associated with the extent of lymph node metastasis, and p-mTOR expression in metastatic lymph nodes is correlated with poor disease-free survival. mTOR may harbor significant potential for a prognostic biomarker and therapeutic target for gastric cancer treatment. © 2009 UICC.