title: Tumor-suppressing pathways in cystic pancreatic tumors.
abstract: OBJECTIVE
  Serous and mucinous cystic pancreatic tumors have different clinical behavior. We evaluated whether they also have genotypic differences by analyses of the tumor suppressor genes, p16INK4a, p53, and DPC4.
  
  
  METHODS
  Seven serous cystadenomas (SCA) and seven malignant mucinous cystadenocarcinomas (MCC) were analyzed for alterations in the tumor suppressor genes p16INK4a, p53, and DPC4 by single-strand conformational variant analysis, direct sequencing, and immunohistochemical analysis. Methylation-specific polymerase chain reaction analysis was performed to identify p16INK4a promoter hypermethylation. Clinical data were compared with genetic data.
  
  
  RESULTS
  None of the seven patients with SCAs but five of the seven patients with MCCs died of the tumor after a median follow-up of 44.5 months (range, 4-169 months). All seven MCCs had alterations in at least one tumor suppressor gene compared with none of the seven SCAs. Of the seven MCCs, three had inactivating p16INK4a promoter hypermethylation, five had p53 alterations, and three had DPC4 mutations.
  
  
  CONCLUSIONS
  The tumor suppressor genes p16INK4a, p53, and appear to play an important role in the tumorigenesis of MCCs but not SCAs. These molecular data underscore the clinical and histologic differences of serous and mucinous cystic pancreatic tumors.
authors.affiliation: Department of General Surgery, Philipps University of Marburg, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Gerdes
authors.forename: Anja
authors.initials: A
authors.lastname: Wild
authors.forename: Judith
authors.initials: J
authors.lastname: Wittenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Barth
authors.forename: Annette
authors.initials: A
authors.lastname: Ramaswamy
authors.forename: Michael
authors.initials: M
authors.lastname: Kersting
authors.forename: Jutta
authors.initials: J
authors.lastname: Lüttges
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Detlef K
authors.initials: DK
authors.lastname: Bartsch
mesh_terms: D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018282:Cystadenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D018807:Polymorphism, Single-Stranded Conformational; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53