title: Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN).
abstract: OBJECTIVE
  Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis.
  
  
  METHODS
  We analysed the expression of p21, p27, p53 and Ki-67, in 210 ductal pancreatic adenocarcinomas, 40 PanIN-3 cases and 40 normal controls combined in a tissue microarray. The results were correlated with clinicopathological and follow-up data.
  
  
  RESULTS
  Our study revealed a differential p27, p21, p53, and Ki-67 expression between ductal adenocarcinoma, PanIN-3 and normal pancreas. p27 expression progressively decreased from normal pancreas to PanIN and to pancreatic cancer. Decreased p27 and increased p53 expression showed a significant association with the T stage. A Ki-67 >5% correlated with reduced survival.
  
  
  CONCLUSIONS
  In pancreatic cancer, loss of p27 and increased p53 expression is associated with a more aggressive phenotype. p27 may play an important role in pancreatic carcinogenesis. A Ki-67 >5% independently predicted poor outcome.
authors.affiliation: Second Department of Pathology, University of Athens, Attikon University Hospital, Haidari, Athens, Greece.
authors.forename: Eva
authors.initials: E
authors.lastname: Karamitopoulou
authors.forename: Inti
authors.initials: I
authors.lastname: Zlobec
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.forename: Vincenza
authors.initials: V
authors.lastname: Carafa
authors.forename: Thomas
authors.initials: T
authors.lastname: Schaffner
authors.forename: Thomas
authors.initials: T
authors.lastname: Brunner
authors.forename: Markus
authors.initials: M
authors.lastname: Borner
authors.forename: Ioannis
authors.initials: I
authors.lastname: Diamantis
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D012372:ROC Curve; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; D016283:Proto-Oncogene Proteins p21(ras)