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ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

Berg, Kasper Drimer ; Vainer, Ben ; Thomsen, Frederik Birkebæk ; Røder, M. Andreas ; Gerds, Thomas Alexander ; Toft, Birgitte Grønkær ; Brasso, Klaus ; Iversen, Peter

European urology, 2014-11, Vol.66 (5), p.851-860 [Periódico revisado por pares]

Kidlington: Elsevier B.V

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Título:
ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer
Autor: Berg, Kasper Drimer ; Vainer, Ben ; Thomsen, Frederik Birkebæk ; Røder, M. Andreas ; Gerds, Thomas Alexander ; Toft, Birgitte Grønkær ; Brasso, Klaus ; Iversen, Peter
Assuntos: Active surveillance ; Aged ; Antigens, Neoplasm ; Biological and medical sciences ; Biomarkers - blood ; Biopsy ; Competing risk ; Digital Rectal Examination ; Disease Progression ; ERG expression ; Gynecology. Andrology. Obstetrics ; Humans ; Male ; Male genital diseases ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Pathology ; Prostate cancer ; Prostate-Specific Antigen ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - pathology ; Risk ; TMPRSS2-ERG ; Trans-Activators - blood ; Transcriptional Regulator ERG ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland ; Urology
É parte de: European urology, 2014-11, Vol.66 (5), p.851-860
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Abstract Background Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed. Objective To examine the association between ERG expression at diagnosis and the risk of progression during AS. Design, setting, and participants This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10–12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. Outcome measurements and statistical analysis Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events. Results and limitations A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression ( p < 0.0001) and of the subgroups PSA progression ( p < 0.0001) and histopathologic progression ( p < 0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7–68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62–3.72; p < 0.0001). The main limitation of this study is its observational nature. Conclusions In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes. Patient summary The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.
Editor: Kidlington: Elsevier B.V
Idioma: Inglês

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ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer

Berg, Kasper Drimer ; Vainer, Ben ; Thomsen, Frederik Birkebæk ; Røder, M. Andreas ; Gerds, Thomas Alexander ; Toft, Birgitte Grønkær ; Brasso, Klaus ; Iversen, Peter

Kidlington: Elsevier B.V

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