PMID- 23544944
OWN - NLM
STAT- MEDLINE
DCOM- 20130708
LR  - 20211203
IS  - 1543-2165 (Electronic)
IS  - 0003-9985 (Linking)
VI  - 137
IP  - 4
DP  - 2013 Apr
TI  - Immunohistochemical expression of phospho-mTOR is associated with poor prognosis 
      in patients with gallbladder adenocarcinoma.
PG  - 552-7
LID - 10.5858/arpa.2012-0032-OA [doi]
AB  - CONTEXT: Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor 
      prognosis and few therapeutic alternatives. The mammalian target of rapamycin 
      (mTOR) is a serine/threonine kinase that plays a central role in cell growth and 
      homeostasis. Its regulation is frequently altered in various tumors and is an 
      attractive target for cancer therapy; however, its status in GBC remains unclear. 
      OBJECTIVE: To characterize immunohistochemical expression and prognostic 
      significance of phospho-mTOR in advanced gallbladder carcinoma. DESIGN: 
      Phospho-mTOR expression was examined by immunohistochemistry in tissue 
      microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, 
      which were divided into 2 groups according to the presence or absence of 
      metaplasia. To evaluate the association of the level of phospho-mTOR expression 
      with clinical variables and patient survival, the advanced GBCs were classified 
      as having low or high expression. Statistical analysis was performed by using a 
      significance level of P < .05, and Kaplan-Meier curves were constructed for 
      survival analysis. RESULTS: Immunostaining for phospho-mTOR was positive in 82 of 
      128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia 
      and 32% with metaplasia) (P < .001). Survival analysis indicated that a high 
      phospho-mTOR immunohistochemical expression was associated with poorer prognosis 
      in patients with advanced GBC (P = .02). CONCLUSIONS: Metaplasia is a common 
      finding in chronic cholecystitis and is considered a precursor lesion of 
      dysplasia. Our results suggest that the activation of mTOR occurs very early 
      during the development of GBC, contributing to the carcinogenesis process. 
      Phospho-mTOR expression is correlated with poor survival, supporting the 
      potential of mTOR for targeted therapy.
FAU - Leal, Pamela
AU  - Leal P
AD  - Department of Pathology, School of Medicine, CEGINBIOREN, University of La 
      Frontera, Temuco, Chile.
FAU - Garcia, Patricia
AU  - Garcia P
FAU - Sandoval, Alejandra
AU  - Sandoval A
FAU - Letelier, Pablo
AU  - Letelier P
FAU - Brebi, Priscilla
AU  - Brebi P
FAU - Ili, Carmen
AU  - Ili C
FAU - Alvarez, Hector
AU  - Alvarez H
FAU - Tapia, Oscar
AU  - Tapia O
FAU - Roa, Juan C
AU  - Roa JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Pathol Lab Med
JT  - Archives of pathology & laboratory medicine
JID - 7607091
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenocarcinoma/*diagnosis/metabolism/mortality
MH  - Aged
MH  - Biomarkers, Tumor/metabolism
MH  - Chile/epidemiology
MH  - Cholecystectomy
MH  - Cholecystitis/diagnosis/metabolism
MH  - Chronic Disease
MH  - Female
MH  - Gallbladder Neoplasms/*diagnosis/metabolism/mortality
MH  - Humans
MH  - Immunohistochemistry/*methods
MH  - Male
MH  - Metaplasia
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Phosphorylation
MH  - Prognosis
MH  - Retrospective Studies
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tissue Array Analysis
EDAT- 2013/04/03 06:00
MHDA- 2013/07/09 06:00
CRDT- 2013/04/03 06:00
PHST- 2013/04/03 06:00 [entrez]
PHST- 2013/04/03 06:00 [pubmed]
PHST- 2013/07/09 06:00 [medline]
AID - 10.5858/arpa.2012-0032-OA [doi]
PST - ppublish
SO  - Arch Pathol Lab Med. 2013 Apr;137(4):552-7. doi: 10.5858/arpa.2012-0032-OA.