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Background  The HER2-HER3 heterodimer significantly decreases survival in breast cancer patients. However, the prognostic value of HER2-HER3 overexpression remains unknown in gastric cancer (GC).    Methods  The expression levels of HER2, HER3, Akt, p-Akt, mTOR and p-mTOR were examined in specimens from 120 GC patients by immunohistochemistry and quantitative reverse transcription-PCR. The associations of HER proteins, PI3K/Akt/mTOR pathway-related proteins, clinicopathological features of GC, and overall survival (OS) were assessed. To comprehensively evaluate the prognostic values of pathway-related proteins, meta-analyses were conducted with STATA 11.0.    Results  HER2 overexpression was significantly associated with HER3 levels ( P  = 0.02). HER3 was highly expressed in gastric cancer tissues. High HER2 and HER3 levels were associated with elevated p-Akt and p-mTOR amounts ( P  < 0.05). Furthermore, HER2-HER3 co-expression was associated with high p-Akt and p-mTOR ( P  < 0.05) levels. Meanwhile, p-mTOR overexpression was tightly associated with differentiation, depth of invasion, lymph node metastasis, TNM stage and OS ( P  < 0.05). By meta-analyses, Akt, p-Akt, and mTOR levels were unrelated to clinicopathological characters. HER3 overexpression was associated with depth of invasion (OR = 2.39, 95%CI 1.62–3.54,  P  < 0.001) and lymph node metastasis (OR = 2.35, 95%CI 1.34–4.11,  P  = 0.003). Further, p-mTOR overexpression was associated with patient age, tumor location, depth of invasion (OR = 1.63, 95%CI 1.08–2.45,  P  = 0.02) and TNM stage (OR = 1.73, 95%CI 1.29–2.32,  P  < 0.001). In addition, HER2-HER3 overexpression corresponded to gradually shortened 5-year OS ( P  < 0.05), and significant relationships were shown among HER3, p-mTOR overexpression, and 1-, 3-, 5-year OS ( P  < 0.05).    Conclusions  HER2-HER3 co-expression may potentially enhance mTOR phosphorylation. HER2-HER3 co-expression and p-mTOR are both related to the prognosis of GC patients.    Electronic supplementary material  The online version of this article (10.1186/s12885-017-3851-y) contains supplementary material, which is available to authorized users.

Positive prognostic value of HER2-HER3 co-expression and p-mTOR in gastric cancer patients