Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low‐risk clear cell renal cell carcinoma

RW Joseph, P Kapur, DJ Serie, JE Eckel‐Passow… - Cancer, 2014 - Wiley Online Library
RW Joseph, P Kapur, DJ Serie, JE Eckel‐Passow, M Parasramka, T Ho, JC Cheville
Cancer, 2014Wiley Online Library
BACKGROUND The majority of patients diagnosed with clear cell renal cell carcinoma
(ccRCC) have low‐risk disease with a< 10% chance of ccRCC‐specific death. DNA
sequencing revealed that mutations in BAP1 (BRCA1 associated protein‐1) occur in 5% to
15% of ccRCC cases and are associated with poor outcomes. The vast majority of BAP1
mutations abolish protein expression. In this study, we used a highly sensitive and specific
immunohistochemistry (IHC) assay to test whether BAP1 expression is an independent …
BACKGROUND
The majority of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have low‐risk disease with a < 10% chance of ccRCC‐specific death. DNA sequencing revealed that mutations in BAP1 (BRCA1 associated protein‐1) occur in 5% to 15% of ccRCC cases and are associated with poor outcomes. The vast majority of BAP1 mutations abolish protein expression. In this study, we used a highly sensitive and specific immunohistochemistry (IHC) assay to test whether BAP1 expression is an independent marker of ccRCC‐specific survival, particularly in patients with low‐risk disease.
METHODS
BAP1 expression was assessed, using IHC, in 1479 patients who underwent nephrectomy to treat clinically localized ccRCC. A centralized pathologist dichotomized patients as either BAP1‐positive or BAP1‐negative. The authors employed Kaplan‐Meier and Cox regression models to associate BAP1 expression with cancer‐specific survival.
RESULTS
A total of 10.5% of tumors were BAP1‐negative, 84.8% of tumors were BAP1‐positive, and 4.6% of tumors had ambiguous staining for BAP1. Patients with BAP1‐negative tumors have an increased risk of ccRCC‐related death (hazard ratio [HR] = 3.06; 95% confidence interval [CI] = 2.28‐4.10; P = 6.77 × 10−14). BAP1 expression remained an independent marker of prognosis after adjusting for the UCLA integrated staging system (UISS) (HR = 1.67; 95% CI = 1.24‐2.25; P < .001). Finally, BAP1 was an independent prognostic marker in low‐risk patients with a Mayo Clinic stage, size, grade, and necrosis (SSIGN) score of ≤ 3 (HR = 3.24; 95% CI = 1.26‐8.33; P = .015).
CONCLUSIONS
This study used a large patient cohort to demonstrate that BAP1 expression is an independent marker of prognosis in patients with low‐risk (SSIGN≤ 3) ccRCC. Cancer 2014;1059–1067. © 2014 American Cancer Society.
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