Dataset Information

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

SUBMITTER: Brooks JD

PROVIDER: S-EPMC5557496 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.

Brooks James D JD Wei Wei W Pollack Jonathan R JR West Robert B RB Shin Jun Ho JH Sunwoo John B JB Hawley Sarah J SJ Auman Heidi H Newcomb Lisa F LF Simko Jeff J Hurtado-Coll Antonio A Troyer Dean A DA Carroll Peter R PR Gleave Martin E ME Lin Daniel W DW Nelson Peter S PS Thompson Ian M IM True Lawrence D LD McKenney Jesse K JK Feng Ziding Z Fazli Ladan L

The Prostate 20160621 15

<h4>Background</h4>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.<h4>Methods</h4>AZGP1 IHC and RISH were performed on a large multi-insti ...[more]

PMID: 27325561

Similar Datasets

Project description:Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors. We used a multi-institutional prostate cancer tissue microarray constructed from radical prostatectomy samples with associated detailed clinical data and with rigorous selection of recurrent and non-recurrent cases to test the prognostic value of immunohistochemistry staining results for the ERG and SPINK1 proteins. In univariate analysis, ERG positive cases (419/1067; 39%) were associated with lower patient age, pre-operative serum PSA levels, lower Gleason scores (? 3+4=7) and improved recurrence free survival (RFS). On multivariate analysis, ERG status was not correlated with RFS, disease specific survival (DSS) or overall survival (OS). High-level SPINK1 protein expression (33/1067 cases; 3%) was associated with improved RFS on univariate and multivariate Cox regression analysis. Over-expression of either protein was not associated with clinical outcome. While expression of ERG and SPINK1 proteins was inversely correlated, it was not mutually exclusive since 3 (0.28%) cases showed high expression of both. While ERG and SPINK1 appear to identify discrete molecular subtypes of prostate cancer, only high expression of SPINK1 was associated with improved clinical outcome. However, by themselves, neither ERG nor SPINK1 appear to be useful biomarkers for prognostication of early stage prostate cancer.

Project description:ObjectiveTo describe the technical aspects and outcomes of robotic-assisted radical prostatectomy (RARP) following abandoned open radical prostatectomy (ORP).Patients and methodsA retrospective review was performed of patients who underwent RARP following abandonment of ORP between 2016 and 2020. RARP was undertaken by two highly experienced robotic surgeons. Analysis of patient and operative characteristics, outcomes, and reasons for abandonment of ORP were described.ResultsSix patients were included for analysis with a median age of 63.5 years [50.3-67.5]. The median body mass index (BMI) was 34.7 [27.8-36.2]. All patients had intermediate-risk prostate cancer. Small prostate and deep pelvis were given as reasons for abandoning ORP in five cases (83.3%), with four of these also attributing increased BMI as a factor. Extensive mesh from previous bilateral inguinal hernia repair was cited as the reason for abandonment in the remaining patient. One patient had commenced androgen deprivation therapy following abandoned ORP. Extensive retropubic adhesions were noted at the time of RARP in five of six patients, with intraoperative complication of small bladder lacerations encountered in the patient with prior mesh hernia repair. The median time from abandoned ORP to RARP was 128 days [40-216]. Median operating time was 160 minutes [139-190] and estimated blood loss was 225 mL [138-375]. Negative margins were obtained in four of six cases, with further salvage treatment being required in one case at a median follow-up duration of 10.5 months [6.5-25.3].ConclusionAbandonment of ORP is an uncommonly reported event, however, in this small case series, we demonstrate that, in the hands of experienced surgeons, RARP is a safe and technically feasible alternative in such cases. Increased BMI, small prostate size and pelvic anatomical constraints appear to be common catalysts for abandonment of open surgery in this cohort. Identifying these high-risk patients early and considering referral to robotic centers may be preferred.

Dataset Information

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.

Publications

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets