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13.02.2019 | Original Article | Ausgabe 11/2019

World Journal of Urology 11/2019

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study

World Journal of Urology > Ausgabe 11/2019
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
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The online version of this article (https://​doi.​org/​10.​1007/​s00345-019-02678-x) contains supplementary material, which is available to authorized users.
Ahmet M. Aydin and Nirmish Singla contributed equally.

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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.

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