Jennifer Cullen1, Denise Young2, Yongmei Chen2, Michael Degon3, James Farrell3, Jason Sedarsky3, Wagner Baptiste3, Philip Rosen3, Vladimir Tolstikov4, Michael Kiebish4, Jacob Kagan5, Sudhir Srivastava5, Huai-Ching Kuo2, Joel T Moncur6, Inger L Rosner3, Niven Narain4, Viatcheslav Akmaev4, Gyorgy Petrovics2, Albert Dobi2, David G McLeod3, Shiv Srivastava2, Isabell A Sesterhenn7. 1. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: jcullen@cpdr.org. 2. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 3. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Walter Reed National Military Medical Center, Urology Service, Bethesda, MD, USA. 4. BERG Health, Framingham, MA, USA. 5. Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA. 6. Walter Reed National Military Medical Center, Urology Service, Bethesda, MD, USA. 7. Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Joint Pathology Center, Silver Spring, MD, USA.
Abstract
BACKGROUND: ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed. OBJECTIVE: This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of CA and AA CaP patients enrolled at Walter Reed National Military Medical Center, who donated clinically annotated, whole-mounted, prostatectomy specimens between 1994 and 2014 following RP, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier (KM) estimation curves and multivariable Cox proportional hazards models were used to examine time to BCR as a function of ERG status, patient race, and obesity. RESULTS AND LIMITATIONS: Among 930 eligible patients (36.1% AA and 63.9% CA), with 155 (16.7%) BCR events and a median follow-up time of 5.1 yr, ERG oncoprotein expression was significantly less prevalent in index tumors of AA versus CA patients (23.2% vs 49.3%; p<0.0001). KM curves showed significantly poorer BCR-free survival for CA patients with ERG-negative index tumors but not for AA patients. Race-stratified multivariable analyses revealed a significant association between ERG-negative index tumors and poorer BCR-free survival among CA patients (hazards ratio=1.67, confidence interval=1.07, 2.61; p=0.024). Less heterogeneity in ERG expression among AA patients may reduce the ability to show its association with BCR. CONCLUSIONS: Striking racial variation in ERG oncoprotein expression was confirmed. A novel observation was the importance of index tumor ERG-negative status in predicting CaP progression for CA patients. PATIENT SUMMARY: ETS-related gene (ERG) typing of tumors may be useful in prognosticating prostate cancer aggressiveness.
BACKGROUND:ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed. OBJECTIVE: This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of CA and AA CaP patients enrolled at Walter Reed National Military Medical Center, who donated clinically annotated, whole-mounted, prostatectomy specimens between 1994 and 2014 following RP, was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier (KM) estimation curves and multivariable Cox proportional hazards models were used to examine time to BCR as a function of ERG status, patient race, and obesity. RESULTS AND LIMITATIONS: Among 930 eligible patients (36.1% AA and 63.9% CA), with 155 (16.7%) BCR events and a median follow-up time of 5.1 yr, ERG oncoprotein expression was significantly less prevalent in index tumors of AA versus CA patients (23.2% vs 49.3%; p<0.0001). KM curves showed significantly poorer BCR-free survival for CA patients with ERG-negative index tumors but not for AA patients. Race-stratified multivariable analyses revealed a significant association between ERG-negative index tumors and poorer BCR-free survival among CA patients (hazards ratio=1.67, confidence interval=1.07, 2.61; p=0.024). Less heterogeneity in ERG expression among AA patients may reduce the ability to show its association with BCR. CONCLUSIONS: Striking racial variation in ERG oncoprotein expression was confirmed. A novel observation was the importance of index tumorERG-negative status in predicting CaP progression for CA patients. PATIENT SUMMARY:ETS-related gene (ERG) typing of tumors may be useful in prognosticating prostate cancer aggressiveness.
Authors: Alba Font-Tello; Núria Juanpere; Silvia de Muga; Marta Lorenzo; José A Lorente; Lluis Fumado; Laia Serrano; Sergio Serrano; Josep Lloreta; Silvia Hernández Journal: Prostate Date: 2015-05-04 Impact factor: 4.104
Authors: Sumin Han; J Chad Brenner; Aaron Sabolch; Will Jackson; Corey Speers; Kari Wilder-Romans; Karen E Knudsen; Theodore S Lawrence; Arul M Chinnaiyan; Felix Y Feng Journal: Neoplasia Date: 2013-10 Impact factor: 5.715
Authors: Rohina Rubicz; Shanshan Zhao; Craig April; Jonathan L Wright; Suzanne Kolb; Ilsa Coleman; Daniel W Lin; Peter S Nelson; Elaine A Ostrander; Ziding Feng; Jian-Bing Fan; Janet L Stanford Journal: Prostate Date: 2015-05-18 Impact factor: 4.104
Authors: Kosj Yamoah; Michael H Johnson; Voleak Choeurng; Farzana A Faisal; Kasra Yousefi; Zaid Haddad; Ashley E Ross; Mohammed Alshalafa; Robert Den; Priti Lal; Michael Feldman; Adam P Dicker; Eric A Klein; Elai Davicioni; Timothy R Rebbeck; Edward M Schaeffer Journal: J Clin Oncol Date: 2015-07-20 Impact factor: 44.544
Authors: Sven Perner; Maria A Svensson; Ruhella R Hossain; John R Day; Jack Groskopf; Ryan C Slaughter; Analee R Jarleborn; Matthias D Hofer; Rainer Kuefer; Francesca Demichelis; David S Rickman; Mark A Rubin Journal: Urology Date: 2010-04 Impact factor: 2.649
Authors: Francesca Khani; Juan Miguel Mosquera; Kyung Park; Mirjam Blattner; Catherine O'Reilly; Theresa Y MacDonald; Zhengming Chen; Abhishek Srivastava; Ashutosh K Tewari; Christopher E Barbieri; Mark A Rubin; Brian D Robinson Journal: Clin Cancer Res Date: 2014-07-23 Impact factor: 12.531
Authors: Philip Rosen; David Pfister; Denise Young; Gyorgy Petrovics; Yongmei Chen; Jennifer Cullen; Diana Böhm; Sven Perner; Albert Dobi; David G McLeod; Isabell A Sesterhenn; Shiv Srivastava Journal: Urology Date: 2012-08-28 Impact factor: 2.649
Authors: Mario Rivera-Izquierdo; Javier Pérez de Rojas; Virginia Martínez-Ruiz; Miguel Ángel Arrabal-Polo; Beatriz Pérez-Gómez; José Juan Jiménez-Moleón Journal: Prostate Cancer Prostatic Dis Date: 2022-01-06 Impact factor: 5.455
Authors: William Gesztes; Cara Schafer; Denise Young; Jesse Fox; Jiji Jiang; Yongmei Chen; Huai-Ching Kuo; Kuwong B Mwamukonda; Albert Dobi; Allen P Burke; Judd W Moul; David G McLeod; Inger L Rosner; Gyorgy Petrovics; Shyh-Han Tan; Jennifer Cullen; Shiv Srivastava; Isabell A Sesterhenn Journal: Sci Rep Date: 2022-03-30 Impact factor: 4.996