title: Disruption of pRb-p16INK4 pathway: a common event in ampullary carcinogenesis.
abstract: OBJECTIVE
  Aberrations of the pRb (Retinoblastoma gene protein)-p16INK4 pathway play a critical role in carcinogenesis. Our objective is to evaluate its role in tumorigenesis and the development of ampullary cancer.
  
  
  METHODS
  We examined expression status of p16INK4 protein and pRb immunohistochemically and assessed their possible prognostic relevance in 36 ampullary cancers.
  
  
  RESULTS
  Thirty-four specimens (94.4%) exhibited alteration of p16INK4 and/or pRb expression, with 63.9% (23/36) of cancers showing p16INK4 negative expression and 94.4% (34/36) pRb abnormal expression. p16INK4 protein negative expression correlated significantly with tumor progression features such as advanced tumor stages (p=0.0291), lymph node metastasis (p=0.005), pancreas invasion (p=0.0002) and duodenum invasion (p=0.0101). Cases with both p16RNK4 protein negative expression and pRb overexpression showed poorer differentiation, more invasive growth (p=0.0425), higher level tumor stages (p=0.0079) and more frequent pancreas invasion (p=0.0024), compared with the others. p16INK4 protein expression showed no relationship with pRb expression (p=0.2199). No association was found in pRb expression status compared with any clinicopathological parameters analyzed.
  
  
  CONCLUSIONS
  The disruption of the pRb-p16NK4 pathway plays an important role in ampullary carcinogenesis, the absence of p16INK4 protein expression might be involved in ampullary tumor progression.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine University of Tokyo, Tokyo, Japan.
authors.forename: Lian-Wen
authors.initials: LW
authors.lastname: Yuan
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Yasujgi
authors.initials: Y
authors.lastname: Seyama
authors.forename: Ya-Zhou
authors.initials: YZ
authors.lastname: Shi
authors.forename: Hirona
authors.initials: H
authors.lastname: Karako
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000378:metabolism* / Q000473:pathology; D003138:Common Bile Duct Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D016160:Retinoblastoma Protein