Endocrine Pathology

, Volume 24, Issue 1, pp 11–19

mTOR is Frequently Active in GH-Secreting Pituitary Adenomas without Influencing their Morphopathological Features

  • Emir Ahmed Sajjad
  • Grzegorz Zieliński
  • Maria Maksymowicz
  • Łukasz Hutnik
  • Tomasz Bednarczuk
  • Paweł Włodarski
Article

DOI: 10.1007/s12022-012-9230-y

Cite this article as:
Sajjad, E.A., Zieliński, G., Maksymowicz, M. et al. Endocr Pathol (2013) 24: 11. doi:10.1007/s12022-012-9230-y

Abstract

Initiating factors and mechanisms of tumor formation are poorly understood in nonfamilial pituitary adenomas. Alteration of intracellular pathways is an underlying event in numerous neoplasms. Among them, excessive activation of mammalian target of rapamycin (mTOR) pathway and its two main regulators, Akt and Erk, has been detected frequently in solid tumors. This study tests the activation of mTOR pathway in pituitary adenomas and its influence on their morphopathological features. Fifty-three pituitary adenomas were fresh frozen after surgery and analyzed by western blotting using phospho-specific antibodies. The impact of Akt and Erk activation on mTOR pathway was assessed in five primary cultures derived from the excised adenomas using selective kinase inhibitors. Statistical correlations of size, volume, Ki-67 %, Knosp’s grading, and somatostatin receptor (SSTR) expression with the activation of mentioned kinases was performed. GHomas showed the highest frequency (71 %) and level of mTOR pathway activity comparing to other adenomas (33 %). No significant correlation was found between mTOR activation and any of the morphopathological features in the studied samples. mTOR kinase phosphorylation was independent of Erk and Akt in primary cultures. Erk activity was significant in all types of adenomas but was the highest in control samples. Its phosphorylation correlated inversely with the Knosp’s grading in nonfunctional pituitary adenomas and directly with somatostatin receptor subtype 2 A expression in GHomas. Presented data point to the noteworthy mTOR activity in GHomas. However, the lack of correlation with morphopathological features, its independence of Erk and Akt phosphorylation, and high level of Erk activity in control pituitary necessitate further research for clarifying the role of these pathways in pituitary adenomas.

Keywords

Pituitary adenoma mTOR Erk Akt Immunohistochemistry 

Supplementary material

12022_2012_9230_MOESM1_ESM.pdf (194 kb)
ESM 1PDF 193 kb
12022_2012_9230_MOESM2_ESM.pdf (17.7 mb)
ESM 2PDF 18,100 kb
12022_2012_9230_MOESM3_ESM.pdf (174 kb)
ESM 3PDF 173 kb

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Emir Ahmed Sajjad
    • 1
  • Grzegorz Zieliński
    • 2
  • Maria Maksymowicz
    • 4
  • Łukasz Hutnik
    • 1
  • Tomasz Bednarczuk
    • 3
  • Paweł Włodarski
    • 1
  1. 1.Department of Histology and Embryology, Center for Biostructure ResearchMedical University of WarsawWarszawaPoland
  2. 2.Department of NeurosurgeryMilitary Institute of MedicineWarszawaPoland
  3. 3.Department of Internal Disease and EndocrinologyMedical University of WarsawWarszawaPoland
  4. 4.Department of PathologyMaria Skłodowska-Curie Institute of OncologyWarszawaPoland

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