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Immunohistochemical Analyses of Mammalian Target of Rapamycin (mTOR) Expression in Pituitary Neuroendocrine Tumors

Ichiro Nakazato1,2, Takayuki Shiomi3, Kenichi Oyama2

  • 1Basic Medical Sciences, International University of Health and Welfare, Graduate School of Medicine, 4-3 Kozunomori, Narita City, Chiba, Japan.

Acta Histochemica Et Cytochemica
|February 6, 2024
PubMed

Insights

Novel treatments are needed for pituitary neuroendocrine tumors (PitNETs) resistant to current therapies. Targeting the mammalian target of rapamycin (mTOR) pathway shows promise for treating growth hormone (GH) and prolactin (PRL)-producing PitNETs.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Pituitary neuroendocrine tumors (PitNETs) present therapeutic challenges, with some cases refractory to standard treatments like medication, surgery, and radiotherapy.
  • The need for novel therapeutic strategies is critical for patients with intractable PitNETs.

Purpose of the Study:

  • To investigate the role of the mammalian target of rapamycin (mTOR) pathway in the development of PitNETs.
  • To identify potential molecular targets for treating PitNETs, particularly those resistant to conventional therapies.

Main Methods:

  • Retrospective analysis of histopathological data from 120 patients with diagnosed PitNETs.
  • Immunohistochemical examination of hormone expression (GH, PRL, etc.) and key molecular markers including phospho-mammalian target of rapamycin (mTOR), somatostatin receptor (SSTR) types 2 and 5, Pit-1, SF-1, and Tpit.

Main Results:

  • A significantly higher percentage of mTOR-positivity was observed in GH-, PRL-, and SSTR5-immunopositive PitNETs compared to their immunonegative counterparts.
  • Activation of the AKT/phosphatidylinositol-3-kinase pathway, including mTOR, is implicated in the pathogenesis of PitNETs, especially those producing GH and PRL.

Conclusions:

  • The mammalian target of rapamycin (mTOR) pathway, particularly its activation, is potentially involved in the development of functional PitNETs.
  • mTOR represents a promising therapeutic target for managing specific types of pituitary neuroendocrine tumors.
Keywords:
immunohistochemistryphospho-mammalian target of rapamycin (mTOR)pituitary neuroendocrine tumor

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