PMID- 22627626
OWN - NLM
STAT- MEDLINE
DCOM- 20120924
LR  - 20220812
IS  - 1309-5730 (Electronic)
IS  - 1018-5615 (Linking)
VI  - 28
IP  - 2
DP  - 2012
TI  - Evidence of ambiguous differentiation and mTOR pathway dysregulation in 
      subependymal giant cell astrocytoma.
PG  - 95-103
LID - 10.5146/tjpath.2012.01107 [doi]
AB  - OBJECTIVE: The exact cell of origin of subependymal giant cell astrocytoma is 
      debated but most currently consider the tumor in the astrocytic category. 
      Mutations and subsequent biallelic inactivation of TSC1 encoding hamartin, or 
      TSC2 encoding tuberin appear to be the underlying genetic aberrations. 
      Inactivation leads to loss of proteins that inhibit mammalian target of rapamycin 
      (mTOR ) disrupting tightly regulated cell functions. MATERIAL AND METHOD: We 
      analyzed the expression of tuberin and hamartin along with an array of 
      neuroepithelial markers in 9 subependymal giant cell astrocytomas. In addition, 
      RPS6 and 4EBP1 regulatory proteins that are downstream in the mTOR pathway were 
      also evaluated. RESULTS: While hamartin and tuberin expression levels were 
      relatively decreased compared to control tissue, this was not of particular 
      practical use to detect the mutated gene since low levels of positivity could be 
      detected throughout the central nervous system. As expected, the levels of RPS6 
      and 4EBP1 were increased, further confirming the activation of the mTOR pathway. 
      GFAP was positive in 5 cases, while Synaptophysin positivity was found in all 
      tumors. CD34 (a marker often observed in well differentiated glio-neuronal 
      tumors), Olig2 (a nuclear marker present in most gliomas), IDH1 and IDH2 were 
      entirely negative in all tumor cells. Ki67 (MIB-1) showed a low proliferation 
      rate ranging from 2% to 8%. CONCLUSION: Staining with neuroepithelial markers 
      supports the suggestion of ambiguous differentiation. Subependymal giant cell 
      astrocytomas do not appear to have the typical expression profiles of astrocytic 
      tumors, under which they have been classified.
FAU - Barrows, Brad D
AU  - Barrows BD
AD  - Department of Pathology, University of California San Francisco, San Francisco, 
      USA.
FAU - Rutkowski, Martin J
AU  - Rutkowski MJ
FAU - Gultekin, Sakir Humayun
AU  - Gultekin SH
FAU - Parsa, Andrew T
AU  - Parsa AT
FAU - Tihan, Tarik
AU  - Tihan T
LA  - eng
PT  - Journal Article
PL  - Turkey
TA  - Turk Patoloji Derg
JT  - Turk patoloji dergisi
JID - 9440471
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, CD34)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (OLIG2 protein, human)
RN  - 0 (Oligodendrocyte Transcription Factor 2)
RN  - 0 (Phosphoproteins)
RN  - 0 (Ribosomal Protein S6)
RN  - 0 (SYP protein, human)
RN  - 0 (Synaptophysin)
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (Vesicular Transport Proteins)
RN  - EC 1.1.1.41 (IDH2 protein, human)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/analysis
MH  - Adolescent
MH  - Adult
MH  - Antigens, CD34/analysis
MH  - Astrocytoma/*chemistry/classification/genetics/*pathology
MH  - Basic Helix-Loop-Helix Transcription Factors/analysis
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Brain Neoplasms/*chemistry/classification/genetics/*pathology
MH  - Cell Cycle Proteins
MH  - *Cell Differentiation
MH  - Child
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Infant
MH  - Isocitrate Dehydrogenase/genetics
MH  - Ki-67 Antigen/analysis
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Nerve Tissue Proteins/analysis
MH  - Oligodendrocyte Transcription Factor 2
MH  - Phosphoproteins/analysis
MH  - Phosphorylation
MH  - Ribosomal Protein S6/analysis
MH  - Signal Transduction
MH  - Synaptophysin
MH  - TOR Serine-Threonine Kinases/*analysis
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/analysis/genetics
MH  - Vesicular Transport Proteins/analysis
EDAT- 2012/05/26 06:00
MHDA- 2012/09/25 06:00
CRDT- 2012/05/26 06:00
PHST- 2012/05/26 06:00 [entrez]
PHST- 2012/05/26 06:00 [pubmed]
PHST- 2012/09/25 06:00 [medline]
AID - 10.5146/tjpath.2012.01107 [doi]
PST - ppublish
SO  - Turk Patoloji Derg. 2012;28(2):95-103. doi: 10.5146/tjpath.2012.01107.