Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.
Given the uncertainties inherent in clinical measures of prostate cancer aggressiveness, clinically validated tissue biomarkers are needed. We tested whether Alpha-2-Glycoprotein 1, Zinc-Binding (AZGP1) protein levels, measured by immunohistochemistry, and RNA expression, by RNA in situ hybridization (RISH), predict recurrence after radical prostatectomy independent of clinical and pathological parameters.



AZGP1 IHC and RISH were performed on a large multi-institutional tissue microarray resource including 1,275 men with 5 year median follow-up. The relationship between IHC and RISH expression levels was assessed using the Kappa analysis. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazards models and the Log-rank test.



Absent or weak expression of AZGP1 protein was associated with worse recurrence free survival (RFS), disease specific survival, and overall survival after radical prostatectomy in univariable analysis. AZGP1 protein expression, along with pre-operative serum PSA levels, surgical margin status, seminal vesicle invasion, extracapsular extension, and Gleason score predicted RFS on multivariable analysis. Similarly, absent or low AZGP1 RNA expression by RISH predicted worse RFS after prostatectomy in univariable and multivariable analysis.



In our large, rigorously designed validation cohort, loss of AZGP1 expression predicts RFS after radical prostatectomy independent of clinical and pathological variables. Prostate 76:1409-1419, 2016. © 2016 Wiley Periodicals, Inc.
Department of Urology, Stanford University, Stanford, California. jdbrooks@stanford.edu.
James D
JD
Brooks
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Wei
W
Wei
Department of Pathology, Stanford University, Stanford, California.
Jonathan R
JR
Pollack
Department of Pathology, Stanford University, Stanford, California.
Robert B
RB
West
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
Jun Ho
JH
Shin
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California.
John B
JB
Sunwoo
Canary Foundation, Canary Center at Stanford, Palo Alto, California.
Sarah J
SJ
Hawley
Canary Foundation, Canary Center at Stanford, Palo Alto, California.
Heidi
H
Auman
Department of Urology, University of Washington Medical Center, Seattle, Washington.
Lisa F
LF
Newcomb
Department of Pathology, University of California San Francisco, San Francisco, California.
Jeff
J
Simko
Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
Antonio
A
Hurtado-Coll
Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.|Eastern Virginia Medical School, Pathology and Microbiology and Molecular Biology, Norfolk, Virginia.
Dean A
DA
Troyer
Department of Urology, University of California San Francisco, San Francisco, California.
Peter R
PR
Carroll
Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
Martin E
ME
Gleave
Department of Urology, University of Washington Medical Center, Seattle, Washington.
Daniel W
DW
Lin
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Peter S
PS
Nelson
Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Ian M
IM
Thompson
Department of Pathology, University of Washington Medical Center, Seattle, Washington.
Lawrence D
LD
True
Department of Pathology, Cleveland Clinic, Cleveland, Ohio.
Jesse K
JK
McKenney
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ziding
Z
Feng
Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
Ladan
L
Fazli
D054392:Adipokines; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis*; D016022:Case-Control Studies; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011897:Random Allocation; D016019:Survival Analysis; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein
AZGP1; immunohistochemistry; prognosis; prostate cancer