PMID- 15835270
OWN - NLM
STAT- MEDLINE
DCOM- 20050524
LR  - 20220318
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 64
IP  - 4
DP  - 2005 Apr
TI  - Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis 
      of the PTEN/AKT/mTOR pathway.
PG  - 341-9
AB  - Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden 
      disease (CD) and germline mutations in the PTEN gene. To further define these 
      relationships, we reviewed clinical and pathologic findings in 31 LDD cases and 
      analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the 
      granule cell hypertrophy in LDD is secondary to activation of mammalian target of 
      rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major 
      regulator of cell growth. Histopathologically, in addition to the classical 
      findings of LDD, we observed prominent vascular proliferation and vacuolization 
      of the white matter in many of the lesions. Four patients met diagnostic criteria 
      for CD, and many of the remaining patients had some clinical features of CD. 
      Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in 
      the large ganglionic cells forming the lesions, indicating activation of the 
      PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis 
      of LDD. These data support recommendations for genetic testing and screening for 
      CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic 
      inhibition of mTOR.
FAU - Abel, Ty W
AU  - Abel TW
AD  - Department of Pathology, Division of Neuropathology, Johns Hopkins University, 
      Baltimore, Maryland 21287, USA. tabel1@jhmi.edu
FAU - Baker, Suzanne J
AU  - Baker SJ
FAU - Fraser, Melissa M
AU  - Fraser MM
FAU - Tihan, Tarik
AU  - Tihan T
FAU - Nelson, James S
AU  - Nelson JS
FAU - Yachnis, Anthony T
AU  - Yachnis AT
FAU - Bouffard, John-Paul
AU  - Bouffard JP
FAU - Mena, Hernando
AU  - Mena H
FAU - Burger, Peter C
AU  - Burger PC
FAU - Eberhart, Charles G
AU  - Eberhart CG
LA  - eng
GR  - K08NS/CA43279/NS/NINDS NIH HHS/United States
GR  - NS44172/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cerebellar Neoplasms/*metabolism/pathology/*physiopathology
MH  - Female
MH  - Ganglioneuroma/*metabolism/pathology/*physiopathology
MH  - Hamartoma Syndrome, Multiple/metabolism/physiopathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - PTEN Phosphohydrolase
MH  - Phosphoric Monoester Hydrolases/genetics/*metabolism
MH  - Protein Kinases/genetics/*metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Thyroid Diseases/metabolism/physiopathology
MH  - Tumor Suppressor Proteins/genetics/*metabolism
RF  - 32
EDAT- 2005/04/20 09:00
MHDA- 2005/05/25 09:00
CRDT- 2005/04/20 09:00
PHST- 2005/04/20 09:00 [pubmed]
PHST- 2005/05/25 09:00 [medline]
PHST- 2005/04/20 09:00 [entrez]
AID - 10.1093/jnen/64.4.341 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2005 Apr;64(4):341-9. doi: 10.1093/jnen/64.4.341.