Immunohistochemical Analysis of mTOR Pathway Expression in Gastric Neuroendocrine TumorsArsenic Ruza1*, Konstantin Griniak2, Lohneis Phillip1, Stephan Felder2, Frank Ulrich Pape3 and Dietel Manfred1
- *Corresponding Author:
- Dr. Ruza Arsenic
Institute of Pathology Charité
University Hospital Berlin, 10117 Berlin, Germany
Tel: 0049 30 450 536 018
E-mail: [email protected]
Received date: March 27, 2014; Accepted date: April 24, 2014; Published date: April 26, 2014
Citation: Ruza A, Griniak K, Phillip L, Felder S, Pape FU, et al. (2014) Immunohistochemical Analysis of mTOR Pathway Expression in Gastric Neuroendocrine Tumors. J Clin Exp Pathol 4:173. doi:10.4172/2161-0681.1000173
Copyright: © 2014 Ruza A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction H2O in any medium, provided the original author and source are credited.
Background: The mammalian target of rapamycin (mTOR) is an important regulator of cell proliferation and protein translation and is activated in various malignancies. Expression of mTOR cascade components in gastric neuroendocrine tumors (NETs), however, has not yet been fully explored.
Aims: The goal of the present study was to assess the activation of mTOR and its upstream and downstream components in gastric NETs using immunohistochemistry and to investigate the relationship between expression and clinicopathological data.
Methods: The expression of phosphorylated mTOR (p-mTOR) and its major target the eukaryotic initiation factor 4E-binding protein 1 (p4EBP1), phospho-phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (pPIK3CA), phospho-protein kinase B (pAkt), phospho-phosphatase and tensin homolog (pPTEN), and phosphotuberous sclerosis 2 (pTSC2) were examined in a series of 35 gastric NETs.
Results: All samples from the 35 patients showed expression of the PI3K catalytic subunit PIK3CA and the mTOR inhibitor TSC2. The p-mTOR was expressed in 88.57%, pPTEN in 97.14%, and pAkt in 65.7% of the examined tumors. The mTOR effector p4E-BP1 was expressed in 88.57% of cases. In addition, the p-mTOR positive rate correlated with Ki-67 expression. In fact, patients with Ki-67 ≤ 2 had higher p-mTOR positive rates (p=0.032); however, no significant correlations between p-mTOR positivity and selected clinicopathological characteristics were observed.
Conclusions: In conclusion, these data demonstrate high mTOR activation in gastric NETs, suggesting that mTOR pathway inhibition may be a possible therapeutic strategy for treatment of gastric NETs.