The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2 -4, P ¼ 0.003), involved lymph nodes (P ¼ 0.010), and tumour stage (I vs II -IV, P ¼ 0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (Po0.001, ¼ 0.035, and o0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P ¼ 0.037) and overall survival (OS, P ¼ 0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P ¼ 0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.

Abstract. Signal transducer and activator of transcription 3 (Stat3), the mammalian target of rapamycin (mtOr) and epidermal growth factor receptor (EGFr), proteins that mediate intracellular signaling related to cell growth, proliferation and differentiation, have received considerable interest as possible targets for cancer treatment. We examined whether the expression of Stat3, mtOr and EGFr correlates with clinicopathological features and patient outcome in gastric cancer. tumor samples were obtained from 126 patients with gastric adenocarcinomas who underwent a radical gastrectomy between 1999 and 2002. the expression of phosphorylated Stat3 (p-Stat3), p-mtOr and EGFr was analyzed by immunohistochemical staining. the relations of these to clinicopathological factors and outcomes were assessed. the expression of p-Stat3 p-mtOr and EGFr positively correlated with the following variables related to tumor progression: the depth of tumor invasion (t1 vs. t2-4; p<0.001, p=0.036 and p<0.001, respectively), lymph node involvement (p=0.008, p=0.027 and p=0.007) and tumor stage (i vs. ii-iV; p<0.001, p=0.041 and p<0.001). the expression of p-STAT3 and EGFR was significantly related to distant metastasis and recurrence (p=0.001 and p=0.039), as well as significantly poorer disease-specific survival (DSS; p=0.0018 and p=0.026). the expression of p-Stat3 was a marginally non-significant prognostic factor for DSS (hazard ratio=2.0, 95% ci 0.91-4.5, p=0.082). increasing expression of p-Stat3, p-mtOr and EGFr was associated with progressively worse dSS. interactions among p-Stat3, p-mtOr and EGFr may play an important role in tumor progression and outcomes in patients with gastric cancer.

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