PMID- 31262501
OWN - NLM
STAT- MEDLINE
DCOM- 20200623
LR  - 20211204
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 17
IP  - 5
DP  - 2019 Oct
TI  - Association of mTOR Pathway Markers and Clinical Outcomes in Patients with 
      Intermediate-/High-risk Prostate Cancer: Long-Term Analysis.
PG  - 366-372
LID - S1558-7673(19)30159-4 [pii]
LID - 10.1016/j.clgc.2019.05.021 [doi]
AB  - INTRODUCTION: The mammalian target of rapamycin (mTOR) pathway is up-regulated in 
      prostate cancer (PCa). We evaluated the tumor tissue expression of downstream 
      mTOR targets in patients with intermediate- and high-risk (IR/HR) PCa and their 
      ability to predict outcome after radical prostatectomy (RP). PATIENTS AND 
      METHODS: Immunohistochemical (IHC) analysis using antibodies against PTEN, mTOR, 
      p-mTOR, pAKT, pS6, and Ki-67 was performed on a tissue microarray constructed 
      from formalin-fixed paraffin-embedded RP specimens. The marker expression was 
      analyzed to determine their predictability for biochemical recurrence (BCR). 
      RESULTS: Tumor tissue from 217 patients (86 IR/131 HR) was analyzed. The most 
      frequent markers were p-mTOR, which was expressed in most cases (85%), whereas 
      PTEN and pS6 were detected in 53% and 40% of the cases, respectively. 
      Overexpression of PTEN (P = .02) and pS6 (P < .001) was associated with HR 
      features. With a median follow up of 13.5 years, 39% (77/196) of patients 
      developed BCR after RP, more frequently (31%) in patients with HR disease (P < 
      .001). Overexpression of pS6 (P = .036), Ki67% (P = .024), and lack of expression 
      of mTOR (P = .021) were associated with BCR. The 5- and 10-year survival rate was 
      81% and 66%, respectively. CONCLUSIONS: Protein expression of downstream mTOR 
      molecules was significantly associated with outcome of patients with IR and HR 
      PCa. Markers of the mTOR pathway could be incorporated in clinical studies 
      evaluating inhibitors of the signaling pathway for treatment selection in men 
      with PCa.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Barata, Pedro C
AU  - Barata PC
AD  - Department of Medicine and Oncology, Tulane University, New Orleans, LA.
FAU - Magi-Galluzzi, Cristina
AU  - Magi-Galluzzi C
AD  - Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Robert 
      J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 
      Cleveland, OH.
FAU - Gupta, Ruby
AU  - Gupta R
AD  - Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, 
      Cleveland, OH.
FAU - Dreicer, Robert
AU  - Dreicer R
AD  - Department of Medicine and Oncology, University of Virginia School of Medicine, 
      Charlottesville, VA.
FAU - Klein, Eric A
AU  - Klein EA
AD  - Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
FAU - Garcia, Jorge A
AU  - Garcia JA
AD  - Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; 
      Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, 
      Cleveland, OH. Electronic address: Garciaj4@ccf.org.
LA  - eng
PT  - Journal Article
DEP - 20190525
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 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  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers, Tumor/metabolism
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/drug therapy/*metabolism/mortality/pathology
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Prognosis
MH  - Prostatic Neoplasms/drug therapy/*metabolism/mortality/pathology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Signal Transduction
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tissue Array Analysis
OTO - NOTNLM
OT  - Biochemical recurrence (BCR)
OT  - PTEN
OT  - mTOR
OT  - pAKT
OT  - pS6
EDAT- 2019/07/03 06:00
MHDA- 2020/06/24 06:00
CRDT- 2019/07/03 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/04/19 00:00 [revised]
PHST- 2019/05/21 00:00 [accepted]
PHST- 2019/07/03 06:00 [pubmed]
PHST- 2020/06/24 06:00 [medline]
PHST- 2019/07/03 06:00 [entrez]
AID - S1558-7673(19)30159-4 [pii]
AID - 10.1016/j.clgc.2019.05.021 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2019 Oct;17(5):366-372. doi: 10.1016/j.clgc.2019.05.021. 
      Epub 2019 May 25.