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The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance

Virchows Archiv volume 465, pages 25–33 (2014)Cite this article

Abstract

Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval, p < 0.05). For survival analyses, the Kaplan–Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (p = 0.02) and tumors with lymph node metastases (p < 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (p = 0.03). Moreover, PI3K (p = 0.004), AKT (p = 0.01), p-AKT (p = 0.01), P70S6K1 (p = 0.04), p-P70S6K1 (p = 0.001), and eIF-4E (p = 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (p = 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Universidad de La Frontera, CEGIN-BIOREN, Temuco, Chile

    Oscar Tapia, Ismael Riquelme, Pamela Leal, Alejandra Sandoval, Susana Aedo, Helga Weber, Pablo Letelier, Enrique Bellolio & Miguel Villaseca

  2. School of Health Sciences, Universidad Católica de Temuco, Temuco, Chile

    Pablo Letelier

  3. Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 377, 8330024, Santiago, Chile

    Patricia Garcia & Juan Carlos Roa

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  1. Oscar Tapia
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Correspondence to Juan Carlos Roa.

Additional information

Oscar Tapia and Ismael Riquelme are both first authors because they contributed equally to the realization of this work.

Founded by FONDECYT Grant No 11110239.

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Tapia, O., Riquelme, I., Leal, P. et al. The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance. Virchows Arch 465, 25–33 (2014). https://doi.org/10.1007/s00428-014-1588-4

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  • DOI: https://doi.org/10.1007/s00428-014-1588-4

Keywords

  • AKT
  • mTOR
  • Immunohistochemistry
  • Gastric cancer