PMID- 29076496
OWN - NLM
STAT- In-Process
LR  - 20181012
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 31
IP  - 1
DP  - 2018 Jan
TI  - Androgen-receptor splice variant-7-positive prostate cancer: a novel molecular
      subtype with markedly worse androgen-deprivation therapy outcomes in newly
      diagnosed patients.
PG  - 198-208
LID - 10.1038/modpathol.2017.74 [doi]
AB  - Androgen-deprivation therapy has been the standard treatment for metastatic and
      locally advanced prostate cancer, but the majority of patients will progress to
      castration-resistant prostate cancer within 2-3 years. Unlike the case in breast 
      cancer, no clinically validated biomarker has been used to predict the outcomes
      of androgen-deprivation therapy. To evaluate androgen-receptor splice variant-7
      (AR-V7) detection in newly diagnosed advanced prostate cancer and describe the
      distinctive prognosis of this novel molecular subtype, this study retrospectively
      enrolled 168 newly diagnosed prostate cancer patients from 2003 to 2015 who
      received androgen-deprivation therapy. AR-V7 immunohistochemical staining was
      performed with a monoclonal antibody, and AR-V7 expression was determined using
      Immune-Reactive Score data. The association between nuclear AR-V7 expression and 
      prognosis was determined. Multiple cause-specific Cox regression and stratified
      cumulative incidences were used to analyze the prognosis risk. Among the 168
      patients, 32 (19%) were AR-V7-positive. Compared with the AR-V7-negative
      patients, the AR-V7-positive patients had significantly lower prostate-specific
      antigen response rates (P<0.001) to androgen-deprivation therapy and a much
      shorter time to castration-resistant prostate cancer (P<0.0001). In Kaplan-Meier 
      analysis, the AR-V7-positive group showed markedly lower castration-resistant
      prostate cancer progression-free survival (P<0.0001) and much lower
      cancer-specific (P<0.0001) and overall survival (P<0.0001) both in all enrolled
      patients and in patients with metastases. AR-V7 positivity was a significant
      predictor of castration-resistant prostate cancer progression in multiple Cox
      regression (hazard ratio: 4.826; 95% CI: 2.960-7.869; P<0.001). AR-V7
      immunohistochemical detection in newly diagnosed prostate cancer patients who are
      planning to receive androgen-deprivation therapy, especially those with
      metastases, is necessary and valuable for prognostic assessment. AR-V7-positive
      prostate cancer should be considered a novel prostate cancer subtype that should 
      be distinguished upon initial biopsy. The main limitation of this study is its
      observational nature.
FAU - Li, Heng
AU  - Li H
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
AD  - Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
FAU - Wang, Zhize
AU  - Wang Z
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
AD  - Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
FAU - Xiao, Wei
AU  - Xiao W
AD  - Translational Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Yan, Libin
AU  - Yan L
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
AD  - Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
FAU - Guan, Wei
AU  - Guan W
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
AD  - Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
FAU - Hu, Zhiquan
AU  - Hu Z
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
AD  - Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
FAU - Wu, Lily
AU  - Wu L
AD  - Department of Molecular and Medical Pharmacology, David Geffen School of
      Medicine, University of California Los Angeles, Los Angeles, CA, USA.
AD  - Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 
      USA.
FAU - Huang, Qihong
AU  - Huang Q
AD  - The Wistar Institute, Philadelphia, PA, USA.
FAU - Wang, Ji
AU  - Wang J
AD  - Department of Cell Death and Cancer Genetics, the Hormel Institute University of 
      Minnesota, Austin, USA.
FAU - Xu, Hua
AU  - Xu H
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
AD  - Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
FAU - Zhang, Xu
AU  - Zhang X
AD  - Department of Urology/State Key Laboratory of Kidney Diseases, Chinese PLA
      General Hospital/PLA Medical School, Beijing, China.
FAU - Ye, Zhangqun
AU  - Ye Z
AD  - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong
      University of Science and Technology, Wuhan, China.
LA  - eng
GR  - P30 CA010815/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171027
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
EDAT- 2017/10/28 06:00
MHDA- 2017/10/28 06:00
CRDT- 2017/10/28 06:00
PHST- 2017/02/28 00:00 [received]
PHST- 2017/05/15 00:00 [accepted]
PHST- 2017/10/28 06:00 [pubmed]
PHST- 2017/10/28 06:00 [medline]
PHST- 2017/10/28 06:00 [entrez]
AID - modpathol201774 [pii]
AID - 10.1038/modpathol.2017.74 [doi]
PST - ppublish
SO  - Mod Pathol. 2018 Jan;31(1):198-208. doi: 10.1038/modpathol.2017.74. Epub 2017 Oct
      27.