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 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 journalReview article

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)
JournalWorld Journal of Urology
DOIs
StatePublished - Jan 1 2019

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BRCA1 Protein
Carcinoma
Neoplasms
Survival
Renal Cell Carcinoma

All Science Journal Classification (ASJC) codes

  • Urology

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Aydin, Ahmet M. ; Singla, Nirmish ; Panwar, Vandana ; Woldu, Solomon L. ; Freifeld, Yuval ; Wood, Christopher G. ; Karam, Jose A. ; Weizer, Alon Z. ; Raman, Jay ; Remzi, Mesut ; Rioux-Leclercq, Nathalie ; Haitel, Andrea ; Roscigno, Marco ; Bolenz, Christian ; Bensalah, Karim ; Westerman, Mary E. ; Sagalowsky, Arthur I. ; Shariat, Shahrokh F. ; Lotan, Yair ; Bagrodia, Aditya ; Kapur, Payal ; Margulis, Vitaly ; Krabbe, Laura Maria. / Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma : a multi-institutional study. In: World Journal of Urology. 2019.
@article{a1c33c72bfdd4cdc89d5f38c79dbf5dd,
title = "Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study",
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.",
author = "Aydin, {Ahmet M.} and Nirmish Singla and Vandana Panwar and Woldu, {Solomon L.} and Yuval Freifeld and Wood, {Christopher G.} and Karam, {Jose A.} and Weizer, {Alon Z.} and Jay Raman and Mesut Remzi and Nathalie Rioux-Leclercq and Andrea Haitel and Marco Roscigno and Christian Bolenz and Karim Bensalah and Westerman, {Mary E.} and Sagalowsky, {Arthur I.} and Shariat, {Shahrokh F.} and Yair Lotan and Aditya Bagrodia and Payal Kapur and Vitaly Margulis and Krabbe, {Laura Maria}",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00345-019-02678-x",
language = "English (US)",
journal = "World Journal of Urology",
issn = "0724-4983",
publisher = "Springer Verlag",

}

Aydin, AM, Singla, N, Panwar, V, Woldu, SL, Freifeld, Y, Wood, CG, Karam, JA, Weizer, AZ, Raman, J, Remzi, M, Rioux-Leclercq, N, Haitel, A, Roscigno, M, Bolenz, C, Bensalah, K, Westerman, ME, Sagalowsky, AI, Shariat, SF, Lotan, Y, Bagrodia, A, Kapur, P, Margulis, V & Krabbe, LM 2019, 'Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study', World Journal of Urology. https://doi.org/10.1007/s00345-019-02678-x

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma : a multi-institutional study. / Aydin, Ahmet M.; Singla, Nirmish; Panwar, Vandana; Woldu, Solomon L.; Freifeld, Yuval; Wood, Christopher G.; Karam, Jose A.; Weizer, Alon Z.; Raman, Jay; Remzi, Mesut; Rioux-Leclercq, Nathalie; Haitel, Andrea; Roscigno, Marco; Bolenz, Christian; Bensalah, Karim; Westerman, Mary E.; Sagalowsky, Arthur I.; Shariat, Shahrokh F.; Lotan, Yair; Bagrodia, Aditya; Kapur, Payal; Margulis, Vitaly; Krabbe, Laura Maria.

In: World Journal of Urology, 01.01.2019.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma

T2 - a multi-institutional study

AU - Aydin, Ahmet M.

AU - Singla, Nirmish

AU - Panwar, Vandana

AU - Woldu, Solomon L.

AU - Freifeld, Yuval

AU - Wood, Christopher G.

AU - Karam, Jose A.

AU - Weizer, Alon Z.

AU - Raman, Jay

AU - Remzi, Mesut

AU - Rioux-Leclercq, Nathalie

AU - Haitel, Andrea

AU - Roscigno, Marco

AU - Bolenz, Christian

AU - Bensalah, Karim

AU - Westerman, Mary E.

AU - Sagalowsky, Arthur I.

AU - Shariat, Shahrokh F.

AU - Lotan, Yair

AU - Bagrodia, Aditya

AU - Kapur, Payal

AU - Margulis, Vitaly

AU - Krabbe, Laura Maria

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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U2 - 10.1007/s00345-019-02678-x

DO - 10.1007/s00345-019-02678-x

M3 - Review article

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JO - World Journal of Urology

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