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

• Published in: Urologic oncology Vol. 36; no. 5; pp. 243.e1 - 243.e8
• Main Authors: da Costa, Walter Henriques, da Cunha, Isabela Werneck, Fares, Aline Fusco, Bezerra, Stephania M., Shultz, Luciana, Clavijo, Diego Abreu, da Silva, Deusdedit Vieira, Netto, George Jabboure, Guimaraes, Gustavo Cardoso, Cassio Zequi, Stenio de
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2018
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - surgery; Female; Follow-Up Studies; Humans; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Kidney Neoplasms - surgery; Male; Middle Aged; Molecular marker; Nephrectomy - mortality; Nuclear Proteins - metabolism; Prognosis; Renal carcinoma; Survival Rate; Transcription Factors - metabolism; Tumor Suppressor Proteins - metabolism; Ubiquitin Thiolesterase - metabolism; Renal carcinoma; Prognosis; Molecular marker
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2018.01.002

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). 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. 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. 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. •PBRM1 and BAP1 genes are frequently mutated in clear cell renal cell carcinoma (ccRCC).•There are few studies evaluating the prognostic impact of such markers tissue expression in early stage ccRCC.•The concomitant negative expression of both markers was associated with poor prognostic parameters.•PBRM1-/BAP1-group presented a higher risk of cancer specific death (HR = 2.722, P = 0.007) and disease recurrence (HR = 2.467, P = 0.004).