PMID- 23084634
OWN - NLM
STAT- MEDLINE
DCOM- 20130507
LR  - 20211203
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Print)
IS  - 0046-8177 (Linking)
VI  - 44
IP  - 4
DP  - 2013 Apr
TI  - Dysregulation of mammalian target of rapamycin pathway in plasmacytoid variant of 
      urothelial carcinoma of the urinary bladder.
PG  - 612-22
LID - S0046-8177(12)00265-1 [pii]
LID - 10.1016/j.humpath.2012.07.009 [doi]
AB  - Plasmacytoid urothelial carcinoma is a rare but aggressive variant of bladder 
      cancer with no clear therapeutic guidelines. Dysregulation of the mammalian 
      target of rapamycin (mTOR) pathway has been linked to oncogenesis in conventional 
      bladder cancer. Several antineoplastic agents targeting mTOR pathway are 
      currently available. This study assesses mTOR pathway status as well as c-myc and 
      p27 expression. We retrieved 19 archival cases of plasmacytoid urothelial 
      carcinoma from two institutions. Whole tissue sections were evaluated for 
      immunoexpression of phosphatase and tensin homolog (PTEN), phosphorylated mTOR, 
      phosphorylated protein kinase B (AKT), phosphorylated S6, c-myc, and p27. We 
      evaluated intensity (0 to 3+) and extent (0%-100%) of expression for all markers. 
      An H score was calculated as the sum of products of intensity and extent for each 
      marker and used during analysis. In addition, PTEN loss was defined as absence of 
      expression in >10% of tumor cells. We encountered PTEN loss in 28%. Higher H 
      score for nuclear phosphorylated AKT and a lower H score for phosphorylated S6 
      was encountered in muscle invasive tumors compared to non-muscle invasive tumors 
      (P = .007 and P = .009, respectively). Although a trend for negative prognostic 
      impact on overall survival for higher phosphorylated mTOR expression was noted (P 
      = .051), markers expression levels failed to predict survival in our cohort. We 
      found dysregulation of mTOR pathway members in urinary bladder plasmacytoid 
      urothelial carcinoma, suggesting that the use of mTOR pathway inhibitors might be 
      beneficial for patients with this aggressive tumor.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Gonzalez-Roibon, Nilda D
AU  - Gonzalez-Roibon ND
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      MD 21231, USA.
FAU - Chaux, Alcides
AU  - Chaux A
FAU - Al-Hussain, Turki
AU  - Al-Hussain T
FAU - Osunkoya, Adeboye O
AU  - Osunkoya AO
FAU - Bezerra, Stephania Martins
AU  - Bezerra SM
FAU - Hicks, Jessica
AU  - Hicks J
FAU - Epstein, Jonathan I
AU  - Epstein JI
FAU - Netto, George J
AU  - Netto GJ
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
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 (Proto-Oncogene Proteins c-akt)
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  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/metabolism
MH  - Carcinoma, Transitional Cell/*metabolism/mortality/pathology
MH  - Female
MH  - Georgia/epidemiology
MH  - Humans
MH  - Male
MH  - Maryland/epidemiology
MH  - Middle Aged
MH  - PTEN Phosphohydrolase/metabolism
MH  - Phosphorylation
MH  - Plasma Cells/*metabolism/pathology
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Urinary Bladder Neoplasms/*metabolism/mortality/pathology
PMC - PMC3742093
MID - NIHMS440717
EDAT- 2012/10/23 06:00
MHDA- 2013/05/08 06:00
PMCR- 2013/08/13
CRDT- 2012/10/23 06:00
PHST- 2012/05/30 00:00 [received]
PHST- 2012/07/10 00:00 [revised]
PHST- 2012/07/11 00:00 [accepted]
PHST- 2012/10/23 06:00 [entrez]
PHST- 2012/10/23 06:00 [pubmed]
PHST- 2013/05/08 06:00 [medline]
PHST- 2013/08/13 00:00 [pmc-release]
AID - S0046-8177(12)00265-1 [pii]
AID - 10.1016/j.humpath.2012.07.009 [doi]
PST - ppublish
SO  - Hum Pathol. 2013 Apr;44(4):612-22. doi: 10.1016/j.humpath.2012.07.009. Epub 2012 
      Oct 17.