title: Loss of nuclear BAP1 protein expression is a marker of poor prognosis in patients with clear cell renal cell carcinoma.
abstract: BRCA1-associated protein 1 (BAP1) is a gene situated on chromosome 3p in a region that is deleted in more than 90% of renal cell carcinomas (RCCs). In the present study, we studied BAP1 immunohistochemical expression in a large series of conventional clear cell RCCs (ccRCCs) treated with radical nephrectomy; we assessed the prognostic value of their expression in terms of patients׳ survival at long-term follow-up.
  
  
  
  A total of 154 consecutive patients with ccRCC were selected from a prospective database and considered for the study purpose; all patients were treated with radical nephrectomy and lymphadenectomy at our Institute of Urology between 1983 and 1985. The features considered in this study were tumor size, grade and stage, vascular and capsular invasion, incidence of metastasis, and patient-specific survival; all these parameters were correlated with immunohistochemical cytoplasmic and nuclear expression of BAP1 in tumoral tissue.
  
  
  
  Median follow-up was 196.18 months and median survival was 125.34 months. Nuclear BAP1 expression showed a high frequency of loss in tumoral cells; nuclear BAP1-negative tumors had higher tumor size, higher Fuhrman grade, and higher stage, a greater amount of vascular and capsular invasion and a higher incidence of metastases. In multivariate analysis, pathological stage and nuclear BAP1 expression resulted independent prognostic factors.
  
  
  
  We have demonstrated that nuclear BAP1 expression is a marker of prognosis in ccRCC, having an influence on cancer-specific survival. The clinical importance for BAP1 will be realized with the identification and application of targeted therapies and with individualized approaches in the adjuvant setting or in the metastatic setting or in both the settings.
authors.affiliation: Dipartimento di Scienze Cliniche e Specialistiche-Sezione di Urologia, Università Politecnica delle Marche-Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy. Electronic address: d.minardi@gostec.net.
authors.forename: Daniele
authors.initials: D
authors.lastname: Minardi
authors.affiliation: Dipartimento di Scienze Cliniche e Molecolari-Sezione di Istologia, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Guendalina
authors.initials: G
authors.lastname: Lucarini
authors.affiliation: Dipartimento di Scienze Cliniche e Specialistiche-Sezione di Urologia, Università Politecnica delle Marche-Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Milanese
authors.affiliation: Dipartimento di Scienze Cliniche e Molecolari-Sezione di Istologia, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Primio
authors.affiliation: Dipartimento di Scienze Biomediche e Sanità Pubblica-Sezione di Patologia e Istopatologia, Università Politecnica delle Marche-Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Dipartimento di Scienze Cliniche e Specialistiche-Sezione di Urologia, Università Politecnica delle Marche-Azienda Ospedaliero-Universitaria Ospedali Riuniti, Ancona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muzzonigro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis; D011446:Prospective Studies; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: C400134:BAP1 protein, human; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1 protein; Cancer-specific survival; Clear cell renal cell carcinoma; Immunohistochemistry