PMID- 22886792
OWN - NLM
STAT- MEDLINE
DCOM- 20130320
LR  - 20211203
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 132
IP  - 6
DP  - 2013 Mar 15
TI  - Loss of pSer2448-mTOR expression is linked to adverse prognosis and tumor 
      progression in ERG-fusion-positive cancers.
PG  - 1333-40
LID - 10.1002/ijc.27768 [doi]
AB  - Prevalence and clinical significance of mammalian target of rapamycin (mTOR) 
      phosphorylation at the serine 2448 is disputed in prostate cancer. A tissue 
      microarray containing 3,261 prostate cancers and 49 normal prostate samples with 
      clinical follow-up data was analyzed for p(Ser2448)-mTOR expression by 
      immunohistochemistry. Moderate to strong p(Ser2448)-mTOR staining was found in 
      all (n = 49) normal prostate tissues, but was lost in 24% or weak in 29% cancers. 
      Moderate and strong staining was found in 36 and 11% of tumors. Loss of 
      p(Ser2448)-mTOR staining was significantly linked to advanced stage (p = 0.0027), 
      high-grade (p = 0.0045), nodal positive cancers (p = 0.0483), early tumor 
      recurrence (p < 0.0001, independently from stage and grade, p = 0.0016), lack of 
      Ets-related gene (ERG) fusion (p < 0.0001), reduced androgen receptor expression 
      (p < 0.0001 each) and increased cell proliferation (p = 0.0092) in all cancers 
      and in the subset of ERG-fusion-positive cancers. Loss of p(Ser2448)-mTOR 
      expression was linked to tumor metastasis (p = 0.0275) in ERG-fusion-positive 
      cancers only. Molecular subset analysis using pre-existing phosphatase and tensin 
      homolog (PTEN) deletion data revealed that loss of p(Ser2448) -mTOR expression is 
      of prognostic relevance and defines a subpopulation of PTEN-deleted and 
      ERG-fusion-positive cancers with a particular poor outcome. The results of our 
      study strongly suggest that loss of p(Ser2448)-mTOR expression is a marker for 
      activated AKT/mTOR signaling. Tumors with concomitant PTEN deletion and activated 
      mTOR signaling indicated by loss of p(Ser2448)-mTOR expression characterize a 
      small (4%) but clinically significant subset of prostate cancers that might 
      optimally benefit from anti-mTOR therapies.
CI  - Copyright (c) 2012 UICC.
FAU - Muller, Julia
AU  - Muller J
AD  - Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Ehlers, Arne
AU  - Ehlers A
FAU - Burkhardt, Lia
AU  - Burkhardt L
FAU - Sirma, Huseyin
AU  - Sirma H
FAU - Steuber, Thomas
AU  - Steuber T
FAU - Graefen, Markus
AU  - Graefen M
FAU - Sauter, Guido
AU  - Sauter G
FAU - Minner, Sarah
AU  - Minner S
FAU - Simon, Ronald
AU  - Simon R
FAU - Schlomm, Thorsten
AU  - Schlomm T
FAU - Michl, Uwe
AU  - Michl U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120830
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (ERG protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Disease Progression
MH  - Gene Deletion
MH  - *Gene Fusion
MH  - Humans
MH  - Male
MH  - PTEN Phosphohydrolase/genetics
MH  - Phosphorylation
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Prostatic Neoplasms/chemistry/*etiology/genetics/pathology
MH  - TOR Serine-Threonine Kinases/analysis/*physiology
MH  - Trans-Activators/*genetics
MH  - Transcriptional Regulator ERG
EDAT- 2012/08/14 06:00
MHDA- 2013/03/21 06:00
CRDT- 2012/08/14 06:00
PHST- 2012/04/19 00:00 [received]
PHST- 2012/07/31 00:00 [accepted]
PHST- 2012/08/14 06:00 [entrez]
PHST- 2012/08/14 06:00 [pubmed]
PHST- 2013/03/21 06:00 [medline]
AID - 10.1002/ijc.27768 [doi]
PST - ppublish
SO  - Int J Cancer. 2013 Mar 15;132(6):1333-40. doi: 10.1002/ijc.27768. Epub 2012 Aug 
      30.