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.
Urologic oncology. 2018 Feb 06 [Epub ahead of print]
Walter Henriques da Costa, Isabela Werneck da Cunha, Aline Fusco Fares, Stephania M Bezerra, Luciana Shultz, Diego Abreu Clavijo, Deusdedit Vieira da Silva, George Jabboure Netto, Gustavo Cardoso Guimaraes, Stenio de Cassio Zequi
Division of Urology, A.C. Camargo Cancer Center, Sao Paulo, Brazil. Electronic address: ., Division of Urology, A.C. Camargo Cancer Center, Sao Paulo, Brazil; National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation., Division of Urology, A.C. Camargo Cancer Center, Sao Paulo, Brazil.