Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression

Richard W. Joseph, Payal Kapur, Daniel J. Serie, Mansi Parasramka, Thai H. Ho, John C. Cheville, Eugene Frenkel, Alexander S. Parker, James Brugarolas

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose In clear cell renal cell carcinoma BAP1 and PBRM1 are 2 of the most commonly mutated genes (10% to 15% and 40% to 50%, respectively). We sought to determine the prognostic significance of PBRM1 and BAP1 expression in clear cell renal cell carcinoma. Materials and Methods We used immunohistochemistry to assess PBRM1 protein expression in 1,479 primary clear cell renal cell carcinoma tumors that were previously stained for BAP1. A centralized pathologist reviewed all cases and categorized tumors as positive or deficient for PBRM1 and BAP1. Kaplan-Meier and Cox regression models were used to evaluate association of PBRM1 and BAP1 expression with the risk of death from renal cell carcinoma and the risk of metastasis after adjustment for age and the Mayo Clinic SSIGN (stage, size, grade and necrosis) score. Results PBRM1 and BAP1 expression was PBRM1+ BAP1+ in 40.1% of tumors, PBRM1- BAP1+ in 48.6%, PBRM1+ BAP1- in 8.7% and PBRM1- BAP1- in 1.8%. The incidence of PBRM1 and BAP1 loss in the same tumor was significantly lower than expected (actual 1.8% vs expected 5.3%, p

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalJournal of Urology
Volume195
Issue number1
DOIs
StatePublished - Jan 1 2016

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Renal Cell Carcinoma
Neoplasms
Proportional Hazards Models
Necrosis
Immunohistochemistry
Neoplasm Metastasis
Incidence
Genes
Proteins

Keywords

  • biological markers
  • carcinoma
  • genes
  • kidney
  • mortality
  • renal cell
  • tumor suppressor

ASJC Scopus subject areas

  • Urology

Cite this

Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression. / Joseph, Richard W.; Kapur, Payal; Serie, Daniel J.; Parasramka, Mansi; Ho, Thai H.; Cheville, John C.; Frenkel, Eugene; Parker, Alexander S.; Brugarolas, James.

In: Journal of Urology, Vol. 195, No. 1, 01.01.2016, p. 180-187.

Research output: Contribution to journalArticle

Joseph, Richard W. ; Kapur, Payal ; Serie, Daniel J. ; Parasramka, Mansi ; Ho, Thai H. ; Cheville, John C. ; Frenkel, Eugene ; Parker, Alexander S. ; Brugarolas, James. / Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression. In: Journal of Urology. 2016 ; Vol. 195, No. 1. pp. 180-187.
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abstract = "Purpose In clear cell renal cell carcinoma BAP1 and PBRM1 are 2 of the most commonly mutated genes (10{\%} to 15{\%} and 40{\%} to 50{\%}, respectively). We sought to determine the prognostic significance of PBRM1 and BAP1 expression in clear cell renal cell carcinoma. Materials and Methods We used immunohistochemistry to assess PBRM1 protein expression in 1,479 primary clear cell renal cell carcinoma tumors that were previously stained for BAP1. A centralized pathologist reviewed all cases and categorized tumors as positive or deficient for PBRM1 and BAP1. Kaplan-Meier and Cox regression models were used to evaluate association of PBRM1 and BAP1 expression with the risk of death from renal cell carcinoma and the risk of metastasis after adjustment for age and the Mayo Clinic SSIGN (stage, size, grade and necrosis) score. Results PBRM1 and BAP1 expression was PBRM1+ BAP1+ in 40.1{\%} of tumors, PBRM1- BAP1+ in 48.6{\%}, PBRM1+ BAP1- in 8.7{\%} and PBRM1- BAP1- in 1.8{\%}. The incidence of PBRM1 and BAP1 loss in the same tumor was significantly lower than expected (actual 1.8{\%} vs expected 5.3{\%}, p",
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