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.
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.
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.
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.
World journal of urology. 2019 Feb 13 [Epub ahead of print]
Ahmet M Aydin, Nirmish Singla, Vandana Panwar, Solomon L Woldu, Yuval Freifeld, Christopher G Wood, Jose A Karam, Alon Z Weizer, Jay D Raman, Mesut Remzi, Nathalie Rioux-Leclercq, Andrea Haitel, Marco Roscigno, Christian Bolenz, Karim Bensalah, Mary E Westerman, Arthur I Sagalowsky, Shahrokh F Shariat, Yair Lotan, Aditya Bagrodia, Payal Kapur, Vitaly Margulis, Laura-Maria Krabbe
Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J8.130, Dallas, TX, 75390-9110, USA., Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Urology, MD Anderson Cancer Center, Houston, TX, USA., Department of Urology, University of Michigan Cancer Center, Ann Arbor, MI, USA., Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA., Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Pathology, Centre Hospitalier Universitaire de Rennes, Rennes, France., Department of Pathology, Medical University Vienna, Vienna, Austria., Department of Urology, Ospedali Riuniti of Bergamo, Bergamo, Italy., Department of Urology, University of Ulm, Ulm, Germany., Department of Urology, Centre Hospitalier Universitaire de Rennes, Rennes, France., Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J8.130, Dallas, TX, 75390-9110, USA. .