BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma

tumor heterogeneity and concordance with paired primary tumor

Jeanette E. Eckel-Passow, Daniel J. Serie, John C. Cheville, Thai H. Ho, Payal Kapur, James Brugarolas, R. Houston Thompson, Bradley C. Leibovich, Eugene D. Kwon, Richard W. Joseph, Alexander S. Parker

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. Materials and methods: We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients. Expression was determined using a validated immunohistochemistry assay, which has been shown to be correlated with mutation status. Results: Of the 97 patients evaluated, 20 and 57% showed loss of BAP1 and PBRM1 in their primary tumors, respectively. Comparing expression across patient-matched primary-metastatic tumor pairs, 98 and 90% had concordant BAP1 and PBRM1 expression, respectively. Both patients who demonstrated discordant BAP1 expression showed loss of BAP1 expression during progression to metastatic ccRCC. Similarly, seven of the ten patients that demonstrated discordant PBRM1 expression showed loss of PBRM1 expression during progression to metastatic ccRCC. We evaluated intra-metastatic tumor heterogeneity using 12 patients who had multiple blocks available from the same tumor with representative pathology; 100 and 92% showed concordant BAP1 and PBRM1 expression, respectively. Amongst 32 patients who had serial metastatic tumors available, both BAP1 and PBRM1 had 97% concordant expression. Conclusions: We observed minimal intra- and inter- tumor heterogeneity in metastatic ccRCC tumors. Patients with discordant BAP1 or PBRM1 expression across their matched primary and metastatic tumors usually showed loss of expression during progression to metastatic ccRCC.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalBMC Urology
Volume17
Issue number1
DOIs
StatePublished - Mar 21 2017

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Neoplasms
Renal Cell Carcinoma
Clear-cell metastatic renal cell carcinoma
Mutation
Immunohistochemistry
Pathology
Proteins

Keywords

  • Clonal
  • Immunohistochemistry
  • Prognostic

ASJC Scopus subject areas

  • Reproductive Medicine
  • Urology

Cite this

BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma : tumor heterogeneity and concordance with paired primary tumor. / Eckel-Passow, Jeanette E.; Serie, Daniel J.; Cheville, John C.; Ho, Thai H.; Kapur, Payal; Brugarolas, James; Thompson, R. Houston; Leibovich, Bradley C.; Kwon, Eugene D.; Joseph, Richard W.; Parker, Alexander S.

In: BMC Urology, Vol. 17, No. 1, 21.03.2017, p. 1-7.

Research output: Contribution to journalArticle

Eckel-Passow, JE, Serie, DJ, Cheville, JC, Ho, TH, Kapur, P, Brugarolas, J, Thompson, RH, Leibovich, BC, Kwon, ED, Joseph, RW & Parker, AS 2017, 'BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor', BMC Urology, vol. 17, no. 1, pp. 1-7. https://doi.org/10.1186/s12894-017-0209-3
Eckel-Passow, Jeanette E. ; Serie, Daniel J. ; Cheville, John C. ; Ho, Thai H. ; Kapur, Payal ; Brugarolas, James ; Thompson, R. Houston ; Leibovich, Bradley C. ; Kwon, Eugene D. ; Joseph, Richard W. ; Parker, Alexander S. / BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma : tumor heterogeneity and concordance with paired primary tumor. In: BMC Urology. 2017 ; Vol. 17, No. 1. pp. 1-7.
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title = "BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor",
abstract = "Background: BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. Materials and methods: We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients. Expression was determined using a validated immunohistochemistry assay, which has been shown to be correlated with mutation status. Results: Of the 97 patients evaluated, 20 and 57{\%} showed loss of BAP1 and PBRM1 in their primary tumors, respectively. Comparing expression across patient-matched primary-metastatic tumor pairs, 98 and 90{\%} had concordant BAP1 and PBRM1 expression, respectively. Both patients who demonstrated discordant BAP1 expression showed loss of BAP1 expression during progression to metastatic ccRCC. Similarly, seven of the ten patients that demonstrated discordant PBRM1 expression showed loss of PBRM1 expression during progression to metastatic ccRCC. We evaluated intra-metastatic tumor heterogeneity using 12 patients who had multiple blocks available from the same tumor with representative pathology; 100 and 92{\%} showed concordant BAP1 and PBRM1 expression, respectively. Amongst 32 patients who had serial metastatic tumors available, both BAP1 and PBRM1 had 97{\%} concordant expression. Conclusions: We observed minimal intra- and inter- tumor heterogeneity in metastatic ccRCC tumors. Patients with discordant BAP1 or PBRM1 expression across their matched primary and metastatic tumors usually showed loss of expression during progression to metastatic ccRCC.",
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T1 - BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma

T2 - tumor heterogeneity and concordance with paired primary tumor

AU - Eckel-Passow, Jeanette E.

AU - Serie, Daniel J.

AU - Cheville, John C.

AU - Ho, Thai H.

AU - Kapur, Payal

AU - Brugarolas, James

AU - Thompson, R. Houston

AU - Leibovich, Bradley C.

AU - Kwon, Eugene D.

AU - Joseph, Richard W.

AU - Parker, Alexander S.

PY - 2017/3/21

Y1 - 2017/3/21

N2 - Background: BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. Materials and methods: We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients. Expression was determined using a validated immunohistochemistry assay, which has been shown to be correlated with mutation status. Results: Of the 97 patients evaluated, 20 and 57% showed loss of BAP1 and PBRM1 in their primary tumors, respectively. Comparing expression across patient-matched primary-metastatic tumor pairs, 98 and 90% had concordant BAP1 and PBRM1 expression, respectively. Both patients who demonstrated discordant BAP1 expression showed loss of BAP1 expression during progression to metastatic ccRCC. Similarly, seven of the ten patients that demonstrated discordant PBRM1 expression showed loss of PBRM1 expression during progression to metastatic ccRCC. We evaluated intra-metastatic tumor heterogeneity using 12 patients who had multiple blocks available from the same tumor with representative pathology; 100 and 92% showed concordant BAP1 and PBRM1 expression, respectively. Amongst 32 patients who had serial metastatic tumors available, both BAP1 and PBRM1 had 97% concordant expression. Conclusions: We observed minimal intra- and inter- tumor heterogeneity in metastatic ccRCC tumors. Patients with discordant BAP1 or PBRM1 expression across their matched primary and metastatic tumors usually showed loss of expression during progression to metastatic ccRCC.

AB - Background: BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. Materials and methods: We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients. Expression was determined using a validated immunohistochemistry assay, which has been shown to be correlated with mutation status. Results: Of the 97 patients evaluated, 20 and 57% showed loss of BAP1 and PBRM1 in their primary tumors, respectively. Comparing expression across patient-matched primary-metastatic tumor pairs, 98 and 90% had concordant BAP1 and PBRM1 expression, respectively. Both patients who demonstrated discordant BAP1 expression showed loss of BAP1 expression during progression to metastatic ccRCC. Similarly, seven of the ten patients that demonstrated discordant PBRM1 expression showed loss of PBRM1 expression during progression to metastatic ccRCC. We evaluated intra-metastatic tumor heterogeneity using 12 patients who had multiple blocks available from the same tumor with representative pathology; 100 and 92% showed concordant BAP1 and PBRM1 expression, respectively. Amongst 32 patients who had serial metastatic tumors available, both BAP1 and PBRM1 had 97% concordant expression. Conclusions: We observed minimal intra- and inter- tumor heterogeneity in metastatic ccRCC tumors. Patients with discordant BAP1 or PBRM1 expression across their matched primary and metastatic tumors usually showed loss of expression during progression to metastatic ccRCC.

KW - Clonal

KW - Immunohistochemistry

KW - Prognostic

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U2 - 10.1186/s12894-017-0209-3

DO - 10.1186/s12894-017-0209-3

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