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Mammalian target of rapamycin expression in poorly differentiated endocrine carcinoma: clinical and therapeutic

Laura Catena1, Emilio Bajetta, Massimo Milione

  • 1Istituto di Oncologia, Policlinico di Monza, Via C. Amati, Monza, MB, Italy. laura.catena@policlinicodimonza.it

Targeted Oncology
|April 7, 2011
PubMed

Insights

Mammalian target of rapamycin (mTOR) is expressed in aggressive poorly differentiated endocrine carcinomas (PDECs). This finding suggests potential therapeutic avenues for PDECs, which are often excluded from clinical trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • The mammalian target of rapamycin (mTOR) pathway is a therapeutic target for well-differentiated endocrine carcinomas using everolimus.
  • Poorly differentiated endocrine carcinomas (PDECs) are aggressive and typically excluded from clinical trials, limiting treatment options.
  • Previous studies on mTOR activity in PDECs were limited to cell lines.

Purpose of the Study:

  • To investigate the expression of mTOR in human poorly differentiated endocrine carcinomas (PDECs).
  • To determine if mTOR expression correlates with tumor origin or proliferation rate in PDECs.

Main Methods:

  • A retrospective review of 36 mono-institutional PDECs was conducted.
  • Immunohistochemistry was used to assess mTOR expression, with normal kidney tissue as a positive control.
  • Antibody specificity was confirmed, and immunoreactivity was scored semi-quantitatively.

Main Results:

  • The primary tumor site in most cases was the pancreas, with 83% of patients presenting at stage IV.
  • mTOR expression was detected in 80% of PDEC samples at consistent levels.
  • No significant relationship was found between mTOR expression and tumor origin or proliferation rate (MIB-1).

Conclusions:

  • mTOR is expressed in human poorly differentiated endocrine carcinomas (PDECs) irrespective of the tumor's primary site.
  • The consistent mTOR expression suggests potential for mTOR-targeted therapies in PDECs.
  • Further studies are needed to confirm the therapeutic efficacy of everolimus in this patient subset.

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