Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma.
OBJECTIVE
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.


METHODS
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.
Herberger
Beata
B
Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Puhalla
Harald
H
Lehnert
Martina
M
Wrba
Fritz
F
Novak
Sabine
S
Brandstetter
Anita
A
Gruenberger
Birgit
B
Gruenberger
Thomas
T
Pirker
Robert
R
Filipits
Martin
M
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D000328:Adult; D000368:Aged; D001661:Biliary Tract Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011494:Protein Kinases / Q000032:analysis*; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases