PMID- 17699857
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20211203
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 13
IP  - 16
DP  - 2007 Aug 15
TI  - Activated mammalian target of rapamycin is an adverse prognostic factor in 
      patients with biliary tract adenocarcinoma.
PG  - 4795-9
AB  - PURPOSE: The mammalian target of rapamycin (mTOR) is a protein kinase that plays 
      a key role in cellular growth and homeostasis. Because its regulation is 
      frequently altered in tumors, mTOR is currently under investigation as a 
      potential target for anticancer therapy. The purpose of our study was to 
      determine the prognostic value of activated mTOR (p-mTOR) in patients with 
      biliary tract adenocarcinoma (BTA), in order to strengthen the rationale for 
      targeted therapy of BTA using mTOR inhibitors. EXPERIMENTAL DESIGN: We determined 
      expression of p-mTOR in paraffin-embedded surgical specimens of BTA by 
      immunohistochemistry with a monoclonal antibody to phosphorylated mTOR. Overall 
      survival was analyzed with a Cox model adjusted for clinical and pathologic 
      factors. RESULTS: Immunostaining for p-mTOR was positive in 56 of 88 (64%) 
      tumors. Activated mTOR was not associated with any of the clinical or pathologic 
      variables of the patients but predicted overall survival of the patients. Overall 
      survival was significantly shorter in patients with p-mTOR-positive tumors as 
      compared with patients with p-mTOR-negative tumors (hazard ratio for death 2.57; 
      95% confidence interval, 1.35-4.89; P = 0.004). Multivariate Cox proportional 
      hazards regression analyses identified p-mTOR to be an independent prognostic 
      factor for death (adjusted hazard ratio for death, 2.44; 95% confidence interval, 
      1.24-4.80; P = 0.01). CONCLUSIONS: Patients with BTA and p-mTOR-positive tumors 
      have a significantly shorter overall survival than patients with p-mTOR-negative 
      tumors and may benefit from targeted therapy with mTOR inhibitors in the future.
FAU - Herberger, Beata
AU  - Herberger B
AD  - Department of Medicine I, Medical University of Vienna, Vienna, Austria.
FAU - Puhalla, Harald
AU  - Puhalla H
FAU - Lehnert, Martina
AU  - Lehnert M
FAU - Wrba, Fritz
AU  - Wrba F
FAU - Novak, Sabine
AU  - Novak S
FAU - Brandstetter, Anita
AU  - Brandstetter A
FAU - Gruenberger, Birgit
AU  - Gruenberger B
FAU - Gruenberger, Thomas
AU  - Gruenberger T
FAU - Pirker, Robert
AU  - Pirker R
FAU - Filipits, Martin
AU  - Filipits M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenocarcinoma/*chemistry/mortality/therapy
MH  - Adult
MH  - Aged
MH  - Biliary Tract Neoplasms/*chemistry/mortality/therapy
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Protein Kinases/*analysis
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases
EDAT- 2007/08/19 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - 13/16/4795 [pii]
AID - 10.1158/1078-0432.CCR-07-0738 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2007 Aug 15;13(16):4795-9. doi: 10.1158/1078-0432.CCR-07-0738.