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

Urologic Oncology: Seminars and Original Investigations Feb 13, 2018

da Costa WH, et al. - An exploration was carried out of the role of immunohistochemical expression of BAP1 and PBRM1 in the prognosis of patients with early stage (pT1–pT2N0M0) clear cell renal cell carcinoma (ccRCC). worse survival rates were illustrated among patients with early-stage tumors with concomitant loss of both PBRM1 and BAP1. The subjects served as a relevant risk group for tumor recurrence and death.

Methods

  • Between 1990 and 2016 researchers selected 441 consecutive patients treated surgically for stages I and II (TNM-AJCC 2010) ccRCC.
  • An appraisal was performed of all cases for uniform reclassification.
  • The most representative tumor areas were selected for the construction of a tissue microarray.
  • A total of 62 patients had frozen tumoral tissue available in the tumor bank of the study institution for quantitative real-time reverse transcriptase polymerase chain reaction analysis.

Results

  • Negative-expression of PBRM1 and BAP1, respectively, was revealed in 91 (20.6%) and 107 (24.3%)-immunostained ccRCC specimens, out of the 441 specimens.
  • Herein, 58 (13.2%) showed negative-expression of both markers (PBRM1-/BAP-).
  • A correlation was illustrated 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).
  • As per the results, both independent PBRM1 and BAP1 negative-expression correlated with lower rates of disease-specific survival and recurrence-free survival.
  • Data disclosed that the disease-specific survival and rates were 95.3% vs 77.6%, respectively (P < 0.001) when patients were grouped into presence of positive expression of one or both markers vs PBRM1-/BAP1- patients.
  • In the multivariate analysis, PBRM1-/BAP1-group demonstrated a higher risk of cancer specific death (hazard ratio = 2.722, P=0.007) and disease recurrence (hazard ratio = 2.467, P=0.004).

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