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 Brugarolas

doi:10.1016/j.juro.2013.09.041

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

J Urol. 2014 Mar;191(3):603-10. doi: 10.1016/j.juro.2013.09.041. Epub 2013 Sep 25.

Authors

Affiliations

¹ Department of Pathology (PK), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology (PK, YL, VM), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Internal Medicine (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Developmental Biology (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center (XJX, JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, Penn State Milton S. Hershey Medical Center (JDR), Hershey, Pennsylvania; Department of Pathology, University of Pittsburgh Medical Center (MTT), Pittsburgh, Pennsylvania; Department of Urology, University of Munich (PN, AB), Munich, Germany; Department of Urology, Paracelsus-Klinik Golzheim, Dusseldorf, Germany (PB); Department of Urology, Central Hospital of Bolzano (CS), Bolzano, Italy; Department of Urology, Medical University of Vienna, Vienna General Hospital (CS, SFS), Vienna, Austria; Department of Urology and Pathology, University of Rennes (KB, NR-L), Rennes, France. Electronic address: payal.kapur@utsouthwestern.edu.
² Department of Pathology (PK), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology (PK, YL, VM), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Internal Medicine (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Developmental Biology (JB), University of Texas Southwestern Medical Center, Dallas, Texas; Simmons Cancer Center (XJX, JB), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, Penn State Milton S. Hershey Medical Center (JDR), Hershey, Pennsylvania; Department of Pathology, University of Pittsburgh Medical Center (MTT), Pittsburgh, Pennsylvania; Department of Urology, University of Munich (PN, AB), Munich, Germany; Department of Urology, Paracelsus-Klinik Golzheim, Dusseldorf, Germany (PB); Department of Urology, Central Hospital of Bolzano (CS), Bolzano, Italy; Department of Urology, Medical University of Vienna, Vienna General Hospital (CS, SFS), Vienna, Austria; Department of Urology and Pathology, University of Rennes (KB, NR-L), Rennes, France.

PMID: 24076305
DOI: 10.1016/j.juro.2013.09.041

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.

Keywords: BAP1 protein; carcinoma; human; kidney; prognosis; renal cell; risk.

Publication types

Multicenter Study

MeSH terms

Aged
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / pathology
Cohort Studies
Female
Follow-Up Studies
Humans
Immunohistochemistry
Kidney Neoplasms / genetics*
Kidney Neoplasms / pathology
Male
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Recurrence, Local
Neoplasm Staging
Predictive Value of Tests
Prognosis
Risk
Tumor Suppressor Proteins / genetics*
Ubiquitin Thiolesterase / genetics*

Substances

BAP1 protein, human
Tumor Suppressor Proteins
Ubiquitin Thiolesterase