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Recent interest has been directed toward BAP1 and PBRM1. In a study specifically assessing immunohistochemistry of BAP1 and PBRM1 among 41 paired samples, there was (i) concordance for BAP1 in 83% of cases compare to 63% for PBRM1, (ii) intratumor heterogeneity among primary tumors in 10% of cases for BAP1 and 24% of PBRM1, (iii) intratumor heterogeneity among metastases in 2% of cases for BAP1 and 7% of cases for PBRM1 . Eckel-Passow et al. also specifically assessed BAP1 and PBRM1 among 111 patients with paired samples who underwent immunohistochemistry . There were 12 patients that had intrametastatic heterogeneity assessed of which there was concordance in 100% of BAP1 specimens and 92% of PBRM1 samples. Thirty-two patients had intermetastatic heterogeneity assessed between 2-4 metastases, with BAP1 concordance in 97% of cases and 97% of PBRM1 cases.
Additional targets for assessing molecular heterogeneity between primary tumors and metastatic sites includes the MET copy number (with potential clinical implications for cabozantinib) and differential expression of PD-L1. Dr. Junker concluded by noting that (i) molecular heterogeneity between primary tumors and metastatic lesions exists, but depends on targets and related biomarkers, (ii) this is important for targeted selection and development of predictive biomarkers, and (iii) intrametastatic heterogeneity was lower compared to primary tumors.
1. Gerlinger M, Rowan AJ, Horswell S, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366(10):883-892.
2. Miura Y, Inoshita N, Ikeda M, et al. Loss of BAP1 protein expression in the first metastatic site predicts prognosis in patients with clear cell renal cell carcinoma. Urol Oncol 2017;35(6):386-391.
3. Eckel-Passow E, Serie DJ, Cheville JC, et al. BAP1 and PBRM1 in metastatic clear cell renal cell carcinoma: Tumor heterogeneity and concordance with paired primary tumor. BMC Urol 2017;17(1):19.
Presented by: Kerstin Junker, Saarland University, Homburg, Germany
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, twitter: @zklaassen_md at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark