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

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 BagrodiaPayal Kapur, Vitaly Margulis, Laura Maria Krabbe

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2419-2427
Number of pages9
JournalWorld journal of urology
Volume37
Issue number11
DOIs
StatePublished - Nov 1 2019

Keywords

  • BAP1 protein
  • Biomarkers
  • Carcinoma
  • Human
  • Prognosis
  • Transitional cell
  • Urinary tract

ASJC Scopus subject areas

  • Urology

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    Aydin, A. M., Singla, N., Panwar, V., Woldu, S. L., Freifeld, Y., Wood, C. G., Karam, J. A., Weizer, A. Z., Raman, J. D., Remzi, M., Rioux-Leclercq, N., Haitel, A., Roscigno, M., Bolenz, C., Bensalah, K., Westerman, M. E., Sagalowsky, A. I., Shariat, S. F., Lotan, Y., ... Krabbe, L. M. (2019). Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study. World journal of urology, 37(11), 2419-2427. https://doi.org/10.1007/s00345-019-02678-x