BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: tumor heterogeneity and concordance with paired primary tumor

BMC Urology

Research Article

Alexander S. Parker¹  Daniel J. Serie¹  Payal Kapur²  Bradley C. Leibovich³  Eugene D. Kwon³  R. Houston Thompson³  Jeanette E. Eckel-Passow⁴  Thai H. Ho⁵  Richard W. Joseph⁶  James Brugarolas⁷  John C. Cheville⁸ 

[1]Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road, 32224, Jacksonville, FL, USA

[2]Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA

[3]Department of Urology, Mayo Clinic, Rochester, MN, USA

[4]Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

[5]Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ, USA

[6]Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA

[7]Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA

[8]Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA

[9]Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

关键词: Clonal;    Prognostic;    Immunohistochemistry;   

DOI  :  10.1186/s12894-017-0209-3

 received in 2016-12-20, accepted in 2017-03-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundBAP1 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 methodsWe 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.ResultsOf 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.ConclusionsWe 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.

【 授权许可】

CC BY   
© The Author(s). 2017