title: Rates of MAGE-A3 and PRAME expressing tumors in FFPE tissue specimens from bladder cancer patients: potential targets for antigen-specific cancer immunotherapeutics.
abstract: BACKGROUND
  Antigen-specific active immunotherapy is an investigational therapeutic approach of potential interest for bladder cancer regardless of disease stage. Clinical development of antigen-specific immunotherapeutics against bladder cancer must be preceded by assessment of the expression of relevant genes in bladder tumors. The objectives of this study (NCT01706185) were to assess the rate of expression of the MAGE-A3 and PRAME genes in bladder tumors and to investigate the feasibility of using formalin-fixed paraffin-embedded (FFPE) tumor tissues for testing.
  
  
  METHODS
  Archived FFPE bladder tumor specimens (any stage) were tested for mRNA expression of MAGE-A3 and PRAME using antigen-specific quantitative reverse transcription polymerase chain reaction assays. Data on patients and tumor characteristics were obtained from hospital records to investigate these characteristics' possible association with the antigen expression.
  
  
  RESULTS
  Over 92% of the 156 tumors examined gave valid antigen test results. Of the tumors with a valid test, 46.5% were MAGE-A3-positive, 32.2% were PRAME-positive and 59.7% positive for at least one of them. Exploratory analyses of possible associations between antigen expression and patient or tumor characteristics did not identify clear associations between antigen expression and any of the variables investigated.
  
  
  CONCLUSIONS
  Assessment of tumor antigen mRNA expression by using FFPE bladder tissues was feasible. The rates of MAGE-A3-positive and PRAME-positive tumors indicate that both antigens may be interesting targets for immunotherapeutics against bladder cancer.
authors.affiliation: Department of Pathology, University Hospitals Leuven Leuven, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.affiliation: Department of Urology, University Hospitals Leuven Leuven, Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.affiliation: Department of Urology, University Hospitals Leuven Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.affiliation: GSK Vaccines Rixensart, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Gruselle
authors.affiliation: GSK Vaccines Rixensart, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Coche
authors.affiliation: Laboratoires Servier Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Therasse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000378:metabolism*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016707:Tissue Fixation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins; C404944:PRAME protein, human; D012333:RNA, Messenger; D005557:Formaldehyde
keywords: Bladder cancer; FFPE samples; MAGE-A3 antigen; PRAME antigen; cancer immunotherapeutics