Zeitschrift für klinische und experimentelle Pathologie

Abstrakt

Immunohistochemical Analysis of mTOR Pathway Expression in Gastric Neuroendocrine Tumors

Arsenic Ruza, Konstantin Griniak, Lohneis Phillip, Stephan Felder, Frank Ulrich Pape and Dietel Manfred

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.