The Impact of PBRM1 Expression as a Prognostic and Predictive Marker in Metastatic Renal Cell Carcinoma

Abstract

PBRM1, a SWI/SNF chromatin remodeling complex gene, is the second most frequently mutated gene in clear cell renal cell carcinoma. Although previous studies showed that loss of PBRM1 expression was associated with poor prognosis of renal cell carcinoma, these studies were performed on earlier stage, surgically resected renal cell carcinoma. Accordingly we investigated the PBRM1 expression profile in patients with stage IV renal cell carcinoma to determine theprognostic and predictive value of PBRM1. A total of 53 patients with stage IV or recurrent renal cell carcinoma were included in analysis. Immunohistochemistry was performed for PBRM1 using formalin fixed, paraffin embedded tissue microarrays. Overall 25 of 53 patients (47%) had high PBRM1 expression in the tumor. On analysis comparing survival rates and treatment responses of patients with renal cell carcinoma high PBRM1 expression in the tumor was associated with reduced overall survival (mean ± SD 45.0 ± 4.8 vs 23.0 ± 8.3months, p = 0.022, and for clear cell renal cell carcinoma 46.0 ± 4.1 vs 27.0 ± 6.7 months, p = 0.053). Regarding treatment outcome higher PBRM1 expression tended to indicate a poorer response to mTOR inhibitor (median progression-free survival 3.0 ± 0.2 vs 1.9 ± 2.3 months, p = 0.101). On subgroup analysis according to the Heng score this trend was more significant in the higher risk group than in the low risk group (progression-free survival for low risk mean 11.6 ± 1.2 vs 7.4 ± 7.4 months, p = 0.157, and for intermediate risk 7.1 ± 24.7 vs 2.9 ± 0.9 months, p = 0.060). Our study shows that the PBRM1 expression level is a potential prognostic marker for advanced renal cell carcinoma. We suggest that determining the tumor PBRM1 expression level may be used to inform the prognosis and treatment of metastatic renal cell carcinoma.