title: Cyclin D1 is a strong prognostic factor for survival in pancreatic cancer: analysis of CD G870A polymorphism, FISH and immunohistochemistry.
abstract: OBJECTIVE
  Cyclin D1 is an important regulator protein for the G1-S cell cycle phase transition. The aim of this trial was to evaluate the impact of the CCND1 polymorphism G870A and corresponding protein expression and CCND1 amplification on the survival of the patients.
  
  
  METHODS
  425 patients with ductal pancreatic adenocarcinoma who underwent resection were included after histopathological confirmation. DNA was analyzed for Cyclin D1 polymorphisms, immunhistochemical examination and fluorescence in situ hybridization analysis of the tumor were performed.
  
  
  RESULTS
  Overall, the mean survival was 22.9 months (20.5-25.3). The survival in patients with Cyclin D1 G870A polymorphism Adenine/Adenine was 15.1 months (95% CI 11.3-18.9), 21.5 months (17.4-25.6) for Adenine/Guanine, and 29.4 months (95% CI 23.8-35.0) for Guanine/Guanine (P = 0.003). A shorter survival was associated with strong/moderate protein expression in immunohistochemistry (IHC) compared to weak/no expression (P = 0.028). Additionally, a significant coherency between unfavourable polymorphism (AA/AG) and increased protein expression was detected (P = 0.005).
  
  
  CONCLUSIONS
  A strong impact on survival of Cyclin D1 G870A polymorphism and the detected corresponding protein expression was found. The biological mechanism of CCND1 in carcinogenesis has not been fully examined; but at present Cyclin D1 seems to be an interesting biomarker for the prognosis of ductal adenocarcinoma.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Bachmann
authors.forename: Anna
authors.initials: A
authors.lastname: Neumann
authors.forename: Andrea
authors.initials: A
authors.lastname: Hinsch
authors.forename: Michael F
authors.initials: MF
authors.lastname: Nentwich
authors.forename: Alexander T
authors.initials: AT
authors.lastname: El Gammal
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Vashist
authors.forename: Daniel
authors.initials: D
authors.lastname: Perez
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Oliver
authors.initials: O
authors.lastname: Mann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000401:mortality* / Q000556:secondary; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D019938:Cyclin D1
keywords: DNA polymorphism; cyclin D; immunhistochemical analysis; pancreatic cancer; prognostic factor