Effective Therapeutic Intervention and Comprehensive Genetic Analysis of mTOR Signaling in PEComa: A Case Report

Anticancer Res. 2015 Jun;35(6):3399-403.

Abstract

Background/aim: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms. The exact genetic alterations underlying the pathophysiology of PEComas are largely unknown, although it has been shown that activation of the Mammalian target of rapamycin (mTOR) signaling pathway plays a pivotal role. Herein we describe the successful treatment of a patient with metastatic PEComa with the mTOR inhibitor everolimus and a comprehensive analysis to identify mechanisms for response.

Materials and methods: Immunohistochemistry, array comparative genomic hybridization (aCGH) and genetic analyses were performed.

Results: Immunohistochemistry confirmed constitutive activation of mTOR. aCGH revealed a hyperdiploid karyotype affecting large regions of the genome. Next-generation sequencing did not reveal any tumor-specific mutations in mTOR-related genes.

Conclusion: Our results show the complexity of determining causal genetic alterations that can predict responsiveness to mTOR inhibition, even for a tumor with a complete remission to this specific treatment.

Keywords: PEC; PEC tumor; PEComa; case report; everolimus; mTOR inhibition; mesenchymal neoplasm; targeted therapy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Comparative Genomic Hybridization
  • Everolimus
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Perivascular Epithelioid Cell Neoplasms / genetics*
  • Perivascular Epithelioid Cell Neoplasms / pathology
  • Remission Induction*
  • Signal Transduction / drug effects
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • Biomarkers, Tumor
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus