title: Pathological Findings of a Subependymal Giant Cell Astrocytoma Following Treatment With Rapamycin.
abstract: BACKGROUND
  Tuberous sclerosis complex is a heritable multisystem disorder associated with genes involved in the formation of a tumor-suppressor complex acting through the Ras homologue enriched in brain protein to limit activation of the mammalian target of rapamycin complex I. Mutations in these genes result in enhanced mammalian target of rapamycin signaling and may cause neurological manifestations including brain tubers, subependymal nodules, and subependymal giant cell astrocytomas. These astrocytomas are tumors that arise near the foramen of Monro and may lead to obstructive hydrocephalus. Standard therapy has been surgical resection. More recently, mammalian target of rapamycin inhibitor, everolimus, has been approved for treatment after demonstration of efficacy in prospective clinical trials.
  
  
  METHODS
  We report a 15 year-old girl with tuberous sclerosis complex who proceeded to surgical resection of her subependymal giant cell astrocytoma after 3 months of treatment with mammalian target of rapamycin inhibition. We compared her subependymal giant cell astrocytoma tissue specimen with 12 untreated subependymal giant cell astrocytomas accessed from The Hospital for Sick Children in Toronto, Canada.
  
  
  RESULTS
  This girl's histopathological findings were consistent with subependymal giant cell astrocytomas with no exposure to mammalian target of rapamycin inhibitors. There were no major differences identified on immunohistochemistry at targets downstream of mammalian target of rapamycin complex 1 or in neighboring signaling pathways. The majority of cells were reactive to glial fibrillary acidic protein, mitogen-activated protein kinase, phospho-S6, caspase 3 (95% positivity), and NP-1.
  
  
  CONCLUSIONS
  In this one individual, rapamycin therapy did not change the histopathological characteristics of subependymal giant cell astrocytoma. Mammalian target of rapamycin inhibition involves complex signaling pathways inducing subependymal giant cell astrocytoma shrinkage. However, its effect is not easily characterized within tumor tissue.
authors.affiliation: Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada; Division of Hematology/Oncology/BMT, British Columbia Children's Hospital, Vancouver, British Columbia, Canada. Electronic address: Sylvia.Cheng@cw.bc.ca.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, Toronto, Canada; The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, Canada; Department of Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.affiliation: Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Ute
authors.initials: U
authors.lastname: Bartels
mesh_terms: D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D009154:Mutation; D020123:Sirolimus / Q000627:therapeutic use*; D014402:Tuberous Sclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020123:Sirolimus
keywords: SEGA; astrocytoma; mTOR inhibitor; tuberous sclerosis