Ahmet M Aydin1,2, Nirmish Singla1, Vandana Panwar3, Solomon L Woldu1, Yuval Freifeld1, Christopher G Wood4, Jose A Karam4, Alon Z Weizer5, Jay D Raman6, Mesut Remzi7, Nathalie Rioux-Leclercq8, Andrea Haitel9, Marco Roscigno10, Christian Bolenz11, Karim Bensalah12, Mary E Westerman1,13, Arthur I Sagalowsky1, Shahrokh F Shariat7, Yair Lotan1, Aditya Bagrodia1, Payal Kapur3, Vitaly Margulis14, Laura-Maria Krabbe1,15. 1. Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J8.130, Dallas, TX, 75390-9110, USA. 2. Department of Urology, Hacettepe University, Ankara, Turkey. 3. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 4. Department of Urology, MD Anderson Cancer Center, Houston, TX, USA. 5. Department of Urology, University of Michigan Cancer Center, Ann Arbor, MI, USA. 6. Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA. 7. Department of Urology, Medical University of Vienna, Vienna, Austria. 8. Department of Pathology, Centre Hospitalier Universitaire de Rennes, Rennes, France. 9. Department of Pathology, Medical University Vienna, Vienna, Austria. 10. Department of Urology, Ospedali Riuniti of Bergamo, Bergamo, Italy. 11. Department of Urology, University of Ulm, Ulm, Germany. 12. Department of Urology, Centre Hospitalier Universitaire de Rennes, Rennes, France. 13. Department of Urology, Mayo Clinic, Rochester, MN, USA. 14. Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J8.130, Dallas, TX, 75390-9110, USA. vitaly.margulis@utsouthwestern.edu. 15. Department of Urology, University of Muenster Medical Center, Muenster, Germany.
Abstract
PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS: BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.
PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS:BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.
Authors: Thomas Seisen; Ross E Krasnow; Joaquim Bellmunt; Morgan Rouprêt; Jeffrey J Leow; Stuart R Lipsitz; Malte W Vetterlein; Mark A Preston; Nawar Hanna; Adam S Kibel; Maxine Sun; Toni K Choueiri; Quoc-Dien Trinh; Steven L Chang Journal: J Clin Oncol Date: 2017-01-03 Impact factor: 44.544
Authors: Richard W Joseph; Payal Kapur; Daniel J Serie; Jeanette E Eckel-Passow; Mansi Parasramka; Thai Ho; John C Cheville; Eugene Frenkel; Dinesh Rakheja; James Brugarolas; Alexander Parker Journal: Cancer Date: 2013-12-30 Impact factor: 6.860
Authors: Tyler J Moss; Yuan Qi; Liu Xi; Bo Peng; Tae-Beom Kim; Nader E Ezzedine; Maribel E Mosqueda; Charles C Guo; Bogdan A Czerniak; Michael Ittmann; David A Wheeler; Seth P Lerner; Surena F Matin Journal: Eur Urol Date: 2017-06-07 Impact factor: 20.096
Authors: Vitaly Margulis; Shahrokh F Shariat; Surena F Matin; Ashish M Kamat; Richard Zigeuner; Eiji Kikuchi; Yair Lotan; Alon Weizer; Jay D Raman; Christopher G Wood Journal: Cancer Date: 2009-03-15 Impact factor: 6.860
Authors: James W F Catto; Abdel-Rahmene Azzouzi; Najla Amira; Ishtiaq Rehman; Kenneth M Feeley; Simon S Cross; Gaelle Fromont; Mathilde Sibony; Freddie C Hamdy; Oliver Cussenot; Mark Meuth Journal: Oncogene Date: 2003-11-27 Impact factor: 9.867