Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma

Thai H. Ho, Payal Kapur, Richard W. Joseph, Daniel J. Serie, Jeanette E. Eckel-Passow, Mansi Parasramka, John C. Cheville, Kevin J. Wu, Eugene P Frenkel, Dinesh Rakheja, Karoliina Stefanius, James B Brugarolas, Alexander S. Parker

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Abstract

BACKGROUND: Recurrent mutations in polybromo-1 (PBRM1, ~40%) and BRCA1-associated protein-1 (BAP1, ~10%) occur in clear cell renal cell carcinoma (ccRCC), but their prevalence in non-ccRCC or renal oncocytoma (RO) is unknown. We evaluated loss of PBRM1 and BAP1 staining in ccRCC, papillary RCC (pRCC), chromophobe RCC (chRCC), and RO tumors using an immunohistochemistry assay in which negative staining was associated with loss-of-function mutations.

METHODS: We identified 458 patients treated surgically for ccRCC, pRCC, chRCC, and RO between 2004 and 2012. We performed immunohistochemistry assays to evaluate PBRM1 and BAP1 protein expression to classify tumors as PBRM1 or BAP1 negative. We compared loss of staining of these 2 proteins in ccRCC and non-ccRCC using the Fisher exact test.

RESULTS: For the total cohort of 458 patients, we successfully stained both PBRM1 and BAP1 in 408 tumor samples. Consistent with the mutation rate, loss of PBRM1 and BAP1 staining occurred in 43% (80/187) and 10% (18/187) of ccRCC cases, respectively. However, loss of PBRM1 staining occurred in only 3% (2/59), 6% (1/17), and 0% (0/34) of pRCC, chRCC, and RO tumors, respectively (P<0.0001). BAP1 loss was not observed in any of the pRCC (n = 61), chRCC (n = 17), or RO (n = 34) tumors, (P = 0.00021).

CONCLUSION: Our data suggest that biallelic inactivation of PBRM1 or BAP1 is less common in non-ccRCC when compared with ccRCC tumors. These findings suggest that loss of PBRM1 or BAP1 are key events in ccRCC, whereas other pathways may support tumorigenesis in non-ccRCC subtypes.

Original languageEnglish (US)
JournalUrologic Oncology
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2015

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Renal Cell Carcinoma
Staining and Labeling
Neoplasms
BRCA1 Protein
Immunohistochemistry
Negative Staining
Mutation
Mutation Rate
Carcinogenesis
Proteins
Renal oncocytoma

Keywords

  • BRCA1-associated protein-1
  • Papillary
  • Polybromo-1
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma. / Ho, Thai H.; Kapur, Payal; Joseph, Richard W.; Serie, Daniel J.; Eckel-Passow, Jeanette E.; Parasramka, Mansi; Cheville, John C.; Wu, Kevin J.; Frenkel, Eugene P; Rakheja, Dinesh; Stefanius, Karoliina; Brugarolas, James B; Parker, Alexander S.

In: Urologic Oncology, Vol. 33, No. 1, 01.01.2015.

Research output: Contribution to journalArticle

Ho, TH, Kapur, P, Joseph, RW, Serie, DJ, Eckel-Passow, JE, Parasramka, M, Cheville, JC, Wu, KJ, Frenkel, EP, Rakheja, D, Stefanius, K, Brugarolas, JB & Parker, AS 2015, 'Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma', Urologic Oncology, vol. 33, no. 1. https://doi.org/10.1016/j.urolonc.2014.10.014
Ho, Thai H. ; Kapur, Payal ; Joseph, Richard W. ; Serie, Daniel J. ; Eckel-Passow, Jeanette E. ; Parasramka, Mansi ; Cheville, John C. ; Wu, Kevin J. ; Frenkel, Eugene P ; Rakheja, Dinesh ; Stefanius, Karoliina ; Brugarolas, James B ; Parker, Alexander S. / Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma. In: Urologic Oncology. 2015 ; Vol. 33, No. 1.
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title = "Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma",
abstract = "BACKGROUND: Recurrent mutations in polybromo-1 (PBRM1, ~40{\%}) and BRCA1-associated protein-1 (BAP1, ~10{\%}) occur in clear cell renal cell carcinoma (ccRCC), but their prevalence in non-ccRCC or renal oncocytoma (RO) is unknown. We evaluated loss of PBRM1 and BAP1 staining in ccRCC, papillary RCC (pRCC), chromophobe RCC (chRCC), and RO tumors using an immunohistochemistry assay in which negative staining was associated with loss-of-function mutations.METHODS: We identified 458 patients treated surgically for ccRCC, pRCC, chRCC, and RO between 2004 and 2012. We performed immunohistochemistry assays to evaluate PBRM1 and BAP1 protein expression to classify tumors as PBRM1 or BAP1 negative. We compared loss of staining of these 2 proteins in ccRCC and non-ccRCC using the Fisher exact test.RESULTS: For the total cohort of 458 patients, we successfully stained both PBRM1 and BAP1 in 408 tumor samples. Consistent with the mutation rate, loss of PBRM1 and BAP1 staining occurred in 43{\%} (80/187) and 10{\%} (18/187) of ccRCC cases, respectively. However, loss of PBRM1 staining occurred in only 3{\%} (2/59), 6{\%} (1/17), and 0{\%} (0/34) of pRCC, chRCC, and RO tumors, respectively (P<0.0001). BAP1 loss was not observed in any of the pRCC (n = 61), chRCC (n = 17), or RO (n = 34) tumors, (P = 0.00021).CONCLUSION: Our data suggest that biallelic inactivation of PBRM1 or BAP1 is less common in non-ccRCC when compared with ccRCC tumors. These findings suggest that loss of PBRM1 or BAP1 are key events in ccRCC, whereas other pathways may support tumorigenesis in non-ccRCC subtypes.",
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TY - JOUR

T1 - Loss of PBRM1 and BAP1 expression is less common in non-clear cell renal cell carcinoma than in clear cell renal cell carcinoma

AU - Ho, Thai H.

AU - Kapur, Payal

AU - Joseph, Richard W.

AU - Serie, Daniel J.

AU - Eckel-Passow, Jeanette E.

AU - Parasramka, Mansi

AU - Cheville, John C.

AU - Wu, Kevin J.

AU - Frenkel, Eugene P

AU - Rakheja, Dinesh

AU - Stefanius, Karoliina

AU - Brugarolas, James B

AU - Parker, Alexander S.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND: Recurrent mutations in polybromo-1 (PBRM1, ~40%) and BRCA1-associated protein-1 (BAP1, ~10%) occur in clear cell renal cell carcinoma (ccRCC), but their prevalence in non-ccRCC or renal oncocytoma (RO) is unknown. We evaluated loss of PBRM1 and BAP1 staining in ccRCC, papillary RCC (pRCC), chromophobe RCC (chRCC), and RO tumors using an immunohistochemistry assay in which negative staining was associated with loss-of-function mutations.METHODS: We identified 458 patients treated surgically for ccRCC, pRCC, chRCC, and RO between 2004 and 2012. We performed immunohistochemistry assays to evaluate PBRM1 and BAP1 protein expression to classify tumors as PBRM1 or BAP1 negative. We compared loss of staining of these 2 proteins in ccRCC and non-ccRCC using the Fisher exact test.RESULTS: For the total cohort of 458 patients, we successfully stained both PBRM1 and BAP1 in 408 tumor samples. Consistent with the mutation rate, loss of PBRM1 and BAP1 staining occurred in 43% (80/187) and 10% (18/187) of ccRCC cases, respectively. However, loss of PBRM1 staining occurred in only 3% (2/59), 6% (1/17), and 0% (0/34) of pRCC, chRCC, and RO tumors, respectively (P<0.0001). BAP1 loss was not observed in any of the pRCC (n = 61), chRCC (n = 17), or RO (n = 34) tumors, (P = 0.00021).CONCLUSION: Our data suggest that biallelic inactivation of PBRM1 or BAP1 is less common in non-ccRCC when compared with ccRCC tumors. These findings suggest that loss of PBRM1 or BAP1 are key events in ccRCC, whereas other pathways may support tumorigenesis in non-ccRCC subtypes.

AB - BACKGROUND: Recurrent mutations in polybromo-1 (PBRM1, ~40%) and BRCA1-associated protein-1 (BAP1, ~10%) occur in clear cell renal cell carcinoma (ccRCC), but their prevalence in non-ccRCC or renal oncocytoma (RO) is unknown. We evaluated loss of PBRM1 and BAP1 staining in ccRCC, papillary RCC (pRCC), chromophobe RCC (chRCC), and RO tumors using an immunohistochemistry assay in which negative staining was associated with loss-of-function mutations.METHODS: We identified 458 patients treated surgically for ccRCC, pRCC, chRCC, and RO between 2004 and 2012. We performed immunohistochemistry assays to evaluate PBRM1 and BAP1 protein expression to classify tumors as PBRM1 or BAP1 negative. We compared loss of staining of these 2 proteins in ccRCC and non-ccRCC using the Fisher exact test.RESULTS: For the total cohort of 458 patients, we successfully stained both PBRM1 and BAP1 in 408 tumor samples. Consistent with the mutation rate, loss of PBRM1 and BAP1 staining occurred in 43% (80/187) and 10% (18/187) of ccRCC cases, respectively. However, loss of PBRM1 staining occurred in only 3% (2/59), 6% (1/17), and 0% (0/34) of pRCC, chRCC, and RO tumors, respectively (P<0.0001). BAP1 loss was not observed in any of the pRCC (n = 61), chRCC (n = 17), or RO (n = 34) tumors, (P = 0.00021).CONCLUSION: Our data suggest that biallelic inactivation of PBRM1 or BAP1 is less common in non-ccRCC when compared with ccRCC tumors. These findings suggest that loss of PBRM1 or BAP1 are key events in ccRCC, whereas other pathways may support tumorigenesis in non-ccRCC subtypes.

KW - BRCA1-associated protein-1

KW - Papillary

KW - Polybromo-1

KW - Renal cell carcinoma

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U2 - 10.1016/j.urolonc.2014.10.014

DO - 10.1016/j.urolonc.2014.10.014

M3 - Article

C2 - 25465300

AN - SCOPUS:84922590453

VL - 33

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

SN - 1078-1439

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