Prognostic impact of concomitant loss of PBRM1 and BAP1 protein expression in early stages of clear cell renal cell carcinoma.

PURPOSE: To evaluate the prognostic impact of immunohistochemical expression of BAP1 and PBRM1 in patients with early stage (pT1-pT2N0M0) clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: A total of 441 consecutive patients treated surgically for stages I and II (TNM-AJCC 2010) ccRCC between 1990 and 2016 were selected. All cases were reviewed for uniform reclassification and the most representative tumor areas were selected for the construction of a tissue microarray. Sixty-two patients had frozen tumoral tissue available in the tumor bank of our institution for quantitative real-time reverse transcriptase polymerase chain reaction analysis. RESULTS: Of the 441-immunostained ccRCC specimens, 91 (20.6%) and 107 (24.3%) showed negative-expression of PBRM1 and BAP1, respectively. Fifty-eight (13.2%) showed negative-expression of both markers (PBRM1-/BAP-). There was an association between both markers expression pattern and classical parameters, such as pT stage (P<0.001), tumor size (P<0.001), and tumor grade (P<0.001). Both independent PBRM1 and BAP1 negative-expression were associated with lower rates of disease-specific survival and recurrence-free survival. When patients were grouped into presence of positive expression of one or both markers vs. PBRM1-/BAP1- patients, disease-specific survival and rates were 95.3% vs. 77.6%, respectively (P<0.001). PBRM1-/BAP1-group presented a higher risk of cancer specific death (hazard ratio = 2.722, P = 0.007) and disease recurrence (hazard ratio = 2.467, P = 0.004) in multivariate analysis. CONCLUSION: Patients with early stage tumors that present concomitant loss of both PBRM1 and BAP1 demonstrated worse survival rates and represent a relevant risk group for tumor recurrence and death.