BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma

Payal Kapur, Alana Christie, Jay D. Raman, Matthew T. Then, Philipp Nuhn, Alexander Buchner, Patrick Bastian, Christian Seitz, Shahrokh F. Shariat, Karim Bensalah, Nathalie Rioux-Leclercq, Xian-Jin Xie, Yair Lotan, Vitaly Margulis, James B Brugarolas

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Abstract

Purpose Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay. Materials and Methods Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes. Results At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8%) experienced recurrence and 121 of 559 (21.6%) had died. BAP1 was negative in 82 of 559 tumors (14.7%). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95% CI 1.8-4.7, p <0.0001) and overall survival (HR 2.0, 95% CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors. Conclusions Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.

Original languageEnglish (US)
Pages (from-to)603-610
Number of pages8
JournalJournal of Urology
Volume191
Issue number3
DOIs
StatePublished - Mar 2014

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Renal Cell Carcinoma
Immunohistochemistry
Neoplasms
Survival
Needle Biopsy
Tumor Suppressor Genes
Nephrectomy
Disease-Free Survival
Necrosis
Regression Analysis
Recurrence
Mutation
Therapeutics

Keywords

  • BAP1 protein
  • carcinoma
  • human
  • kidney
  • prognosis
  • renal cell
  • risk

ASJC Scopus subject areas

  • Urology

Cite this

BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma. / Kapur, Payal; Christie, Alana; Raman, Jay D.; Then, Matthew T.; Nuhn, Philipp; Buchner, Alexander; Bastian, Patrick; Seitz, Christian; Shariat, Shahrokh F.; Bensalah, Karim; Rioux-Leclercq, Nathalie; Xie, Xian-Jin; Lotan, Yair; Margulis, Vitaly; Brugarolas, James B.

In: Journal of Urology, Vol. 191, No. 3, 03.2014, p. 603-610.

Research output: Contribution to journalArticle

Kapur, P, Christie, A, Raman, JD, Then, MT, Nuhn, P, Buchner, A, Bastian, P, Seitz, C, Shariat, SF, Bensalah, K, Rioux-Leclercq, N, Xie, X-J, Lotan, Y, Margulis, V & Brugarolas, JB 2014, 'BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma', Journal of Urology, vol. 191, no. 3, pp. 603-610. https://doi.org/10.1016/j.juro.2013.09.041
Kapur, Payal ; Christie, Alana ; Raman, Jay D. ; Then, Matthew T. ; Nuhn, Philipp ; Buchner, Alexander ; Bastian, Patrick ; Seitz, Christian ; Shariat, Shahrokh F. ; Bensalah, Karim ; Rioux-Leclercq, Nathalie ; Xie, Xian-Jin ; Lotan, Yair ; Margulis, Vitaly ; Brugarolas, James B. / BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma. In: Journal of Urology. 2014 ; Vol. 191, No. 3. pp. 603-610.
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title = "BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma",
abstract = "Purpose Mutations in the tumor suppressor gene BAP1 occur in approximately 15{\%} of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay. Materials and Methods Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes. Results At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8{\%}) experienced recurrence and 121 of 559 (21.6{\%}) had died. BAP1 was negative in 82 of 559 tumors (14.7{\%}). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95{\%} CI 1.8-4.7, p <0.0001) and overall survival (HR 2.0, 95{\%} CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors. Conclusions Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.",
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author = "Payal Kapur and Alana Christie and Raman, {Jay D.} and Then, {Matthew T.} and Philipp Nuhn and Alexander Buchner and Patrick Bastian and Christian Seitz and Shariat, {Shahrokh F.} and Karim Bensalah and Nathalie Rioux-Leclercq and Xian-Jin Xie and Yair Lotan and Vitaly Margulis and Brugarolas, {James B}",
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T1 - BAP1 immunohistochemistry predicts outcomes in a multi-institutional cohort with clear cell renal cell carcinoma

AU - Kapur, Payal

AU - Christie, Alana

AU - Raman, Jay D.

AU - Then, Matthew T.

AU - Nuhn, Philipp

AU - Buchner, Alexander

AU - Bastian, Patrick

AU - Seitz, Christian

AU - Shariat, Shahrokh F.

AU - Bensalah, Karim

AU - Rioux-Leclercq, Nathalie

AU - Xie, Xian-Jin

AU - Lotan, Yair

AU - Margulis, Vitaly

AU - Brugarolas, James B

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N2 - Purpose Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay. Materials and Methods Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes. Results At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8%) experienced recurrence and 121 of 559 (21.6%) had died. BAP1 was negative in 82 of 559 tumors (14.7%). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95% CI 1.8-4.7, p <0.0001) and overall survival (HR 2.0, 95% CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors. Conclusions Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.

AB - Purpose Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay. Materials and Methods Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes. Results At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8%) experienced recurrence and 121 of 559 (21.6%) had died. BAP1 was negative in 82 of 559 tumors (14.7%). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95% CI 1.8-4.7, p <0.0001) and overall survival (HR 2.0, 95% CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors. Conclusions Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.

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KW - human

KW - kidney

KW - prognosis

KW - renal cell

KW - risk

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