title: ΔNp63 expression is a protective factor of progression in clinical high grade T1 bladder cancer.
abstract: OBJECTIVE
  Several risk factors have been claimed to predict the progression of clinically high grade T1 bladder tumors. However, these factors are not specific enough to define which patients should be treated immediately with radical cystectomy. Therefore, it is critical to identify molecular markers that can help provide individualized, risk stratified decision making. Our main goal was to evaluate the role of total p63, p53 and ΔNp63 expression in cases of clinically high grade T1 bladder cancer progression.
  
  
  METHODS
  Total p63, p53 and ΔNp63 expression was analyzed by immunohistochemistry in 134 clinically high grade T1 tumors. We assessed clinical progression to muscle invasive disease or radical cystectomy as a patient outcome end point. Survival analysis was done for recurrence-free, progression-free, disease specific and overall survival.
  
  
  RESULTS
  A total of 132 patients (98.5%) underwent repeat transurethral resection. Cases of early progression (less than 3 months) were excluded from study to avoid under staging. Of the tumors 90 (67.2%) showed ΔNp63 expression loss. During a median followup of 62.1 months 19 patients (14.2%) progressed to muscle invasive disease. The progression rate was 21.1% in patients with tumors characterized by ΔNp63 loss but no progression was observed in those with tumors with ΔNp63 expression (p <0.001). There was no difference in the number of patients who underwent repeat transurethral resection, had associated carcinoma in situ, showed lymphovascular invasion or received followup intravesical bacillus Calmette-Guérin courses.
  
  
  CONCLUSIONS
  ΔNp63 expression is a favorable prognostic factor in clinically high grade T1 bladder cancer. This marker identifies patients at low risk for progression who could benefit from conservative therapy with transurethral bladder tumor resection and bacillus Calmette-Guérin, avoiding over treatment with immediate radical cystectomy.
authors.affiliation: Department of Pathology, Columbia University, New York, New York; Department of Urology, Columbia University, New York, New York; Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gaya
authors.affiliation: Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: López-Martínez
authors.affiliation: Department of Pathology, Columbia University, New York, New York; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Orit
authors.initials: O
authors.lastname: Karni-Schmidt
authors.affiliation: Department of Pathology, Columbia University, New York, New York; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Bonal
authors.affiliation: Department of Pathology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Algaba
authors.affiliation: Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Palou
authors.affiliation: Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Humberto
authors.initials: H
authors.lastname: Villavicencio
authors.affiliation: Department of Urology, Columbia University, New York, New York.
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
authors.affiliation: Department of Pathology, Columbia University, New York, New York; Department of Urology, Columbia University, New York, New York; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: carlos.cordon-cardo@mssm.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.affiliation: Department of Pathology, Columbia University, New York, New York; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: mireia.castillo-martin@mssm.edu.
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo-Martin
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D060787:Neoplasm Grading; D065840:Protective Factors; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: TP63 protein; biological markers; disease progression; human; prognosis; urinary bladder neoplasms