PMID- 23623586
OWN - NLM
STAT- MEDLINE
DCOM- 20131031
LR  - 20220311
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 44
IP  - 9
DP  - 2013 Sep
TI  - Relevance of the mammalian target of rapamycin pathway in the prognosis of 
      patients with high-risk non-muscle invasive bladder cancer.
PG  - 1766-72
LID - S0046-8177(13)00078-6 [pii]
LID - 10.1016/j.humpath.2012.11.026 [doi]
AB  - High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher 
      rates of recurrence and progression. Molecular markers within aberrant signaling 
      pathways in cancer need further evaluation of their role as prognostic indicators 
      and potential future targets for prevention of recurrence. Our objective was to 
      investigate the role of the mammalian target of rapamycin (mTOR) signaling 
      pathway on the stage and outcome of patients with high-risk NMIBC. Tissue 
      microarrays were built from archival bladder tumor specimens (n = 142). Various 
      clinicopathologic variables were collected retrospectively from patients treated 
      with transurethral resection. Immunohistochemical staining was performed for 
      phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, 
      phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding 
      protein-1, and p27. Multivariate analysis using Cox regression models addressed 
      recurrence-free survival (RFS), progression-free survival, and worsening-free 
      survival. In multivariate analysis, p-S6 was an independent predictor of shorter 
      RFS (hazard ratio, 3.55; 95% CI, 1.31-9.64). Expression of p27 was inversely 
      correlated with RFS (hazard ratio, 0.27; 95% CI, 0.10-0.74). Low levels of 
      phosphatase and tensin homolog expression were associated with worsening-free 
      survival (P < .03). None of the markers showed correlation with progression-free 
      survival. Our results demonstrate that activation of the mTOR pathway, as 
      assessed by p-S6 and expression of p27, might be used to provide prognostic 
      information, particularly as a predictor of recurrence among patients with 
      high-risk NMIBC.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Fahmy, Mona
AU  - Fahmy M
AD  - McGill Urologic Oncology Research, Division of Urology, McGill University Health 
      Center and Research Institute, Montreal, Canada H3G 1A4.
FAU - Mansure, Jose Joao
AU  - Mansure JJ
FAU - Brimo, Fadi
AU  - Brimo F
FAU - Yafi, Faysal A
AU  - Yafi FA
FAU - Segal, Robert
AU  - Segal R
FAU - Althunayan, Abdulaziz
AU  - Althunayan A
FAU - Hicks, Jessica
AU  - Hicks J
FAU - Meeker, Alan
AU  - Meeker A
FAU - Netto, George
AU  - Netto G
FAU - Kassouf, Wassim
AU  - Kassouf W
LA  - eng
GR  - MOP 89796/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130423
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
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  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/metabolism
MH  - Carcinoma in Situ/metabolism/mortality/*pathology
MH  - Carcinoma, Transitional Cell/metabolism/mortality/*secondary
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tissue Array Analysis
MH  - Urinary Bladder Neoplasms/metabolism/mortality/*pathology
OTO - NOTNLM
OT  - High-risk non-muscle invasive bladder cancer
OT  - Prognosis
OT  - Tissue microarray
OT  - mTOR pathway
EDAT- 2013/04/30 06:00
MHDA- 2013/11/01 06:00
CRDT- 2013/04/30 06:00
PHST- 2012/09/16 00:00 [received]
PHST- 2012/11/12 00:00 [revised]
PHST- 2012/11/13 00:00 [accepted]
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2013/11/01 06:00 [medline]
AID - S0046-8177(13)00078-6 [pii]
AID - 10.1016/j.humpath.2012.11.026 [doi]
PST - ppublish
SO  - Hum Pathol. 2013 Sep;44(9):1766-72. doi: 10.1016/j.humpath.2012.11.026. Epub 2013 
      Apr 23.