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01-11-2019 | Urothelial Cancer | Original Article

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

Authors: 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

Published in: World Journal of Urology | Issue 11/2019

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.

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Title: Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study
Authors: 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
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Urothelial Cancer
Urothelial Cancer
Published in: World Journal of Urology / Issue 11/2019
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-019-02678-x

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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