Volume 66, Issue 5, Pages 851-860 (November 2014) ERG Protein Expression in Diagnostic Specimens Is Associated with Increased Risk of Progression During Active Surveillance for Prostate Cancer  Kasper Drimer Berg, Ben Vainer, Frederik Birkebæk Thomsen, M. Andreas Røder, Thomas Alexander Gerds, Birgitte Grønkær Toft, Klaus Brasso, Peter Iversen  European Urology  Volume 66, Issue 5, Pages 851-860 (November 2014) DOI: 10.1016/j.eururo.2014.02.058 Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 1 (a, c, e) Haematoxylin and eosin (H&E) staining and (b, d, f) immunohistochemical (IHC) staining for ERG protein in three representative biopsy cores. (a) H&E stain in benign glands; (b) negative IHC stain for ERG protein in benign glands in the same case as (a); (c) H&E stain in malignant glands; (d) negative IHC stain for ERG protein in malignant glands in the same case as (c); (e) H&E stain in malignant glands; (f) positive IHC stain for ERG protein in malignant glands in the same case as (e). Note that benign endothelial cells as well as immune cells stain positive for ERG protein and are used as an internal control for the staining procedure. Original magnification: ×100. B=benign glands; M=malignant glands; V=vessel; asterisk indicates immune cells. European Urology 2014 66, 851-860DOI: (10.1016/j.eururo.2014.02.058) Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 2 The cumulative incidence of (a) overall active surveillance (AS) progression; (b) histopathologic progression; (c) clinical progression; and (d) prostate-specific antigen (PSA) progression during AS. Competing events are curatively intended treatment, watchful waiting, and death—all without progression for the analysed progression criterion. Patients are stratified according to ERG status at diagnosis. The p values for log-rank and Gray's tests are added. For ERG-negative versus ERG-positive patients, the 2-yr cumulative incidence of (a) overall AS progression was 21.7% (95% confidence interval [CI], 14.3–29.1) versus 58.6% (95% CI, 48.7–68.5); (b) histopathologic progression was 10.1% (95% CI, 4.7–15.5) versus 39.8% (95% CI, 30.0–49.6); (c) clinical progression was 4.2% (95% CI, 0.6–7.8) versus 10.6% (95% CI, 4.4–16.7); and (d) PSA progression was 11.6% (95% CI, 5.9–17.4) versus 31.4% (95% CI, 22.1–40.8). European Urology 2014 66, 851-860DOI: (10.1016/j.eururo.2014.02.058) Copyright © 2014 European Association of Urology Terms and Conditions

Fig. 3 The effect of ERG status on the predicted risk of overall active surveillance (AS) progression within 2 yr of AS, based on a model with age, prostate-specific antigen density, percentage of positive biopsies, maximum tumour involvement in any single core, diagnostic Gleason score, and cT stage (x-axis) versus an expanded model also including ERG status at diagnosis (y-axis). The calibration of our model showed high agreement between predicted and observed probabilities of overall AS progression within 2 yr. When ERG status was included in the model, a lower prediction error was found compared with the reference model throughout the study period. Likewise, the model including ERG status at diagnosis showed a higher change in discrimination ability (c-index) throughout the study period. European Urology 2014 66, 851-860DOI: (10.1016/j.eururo.2014.02.058) Copyright © 2014 European Association of Urology Terms and Conditions