title: Molecular Characteristics of Pancreatic Ductal Adenocarcinomas with High-Grade Pancreatic Intraepithelial Neoplasia (PanIN) Are Different from Those without High-Grade PanIN.
abstract: OBJECTIVE
  We reported that pancreatic ductal adenocarcinomas (PDACs) without high-grade pancreatic intraepithelial neoplasia (PanIN) in the vicinity had worse prognoses than PDACs with high-grade PanIN. However, the molecular characteristics of PDACs with and without high-grade PanIN have not been compared. The aim of this study is to clarify the molecular characteristics of PDACs with and without high-grade PanIN.
  
  
  RESULTS
  We reviewed all of a consecutive series of 100 patients with PDACs and divided them into 2 groups: the PDACs with PanIN-2 or PanIN-3 in the background (the PanIN-high group, n = 60) and the PDACs without PanIN-2 or PanIN-3 in the background (the PanIN-low group, n = 40). We evaluated the p53, p16, and SMAD4 expressions in the invasive ductal carcinoma (IDC) components by immunohistochemical staining. KRAS mutation was also analyzed in 80 tumors. The PanIN-low group showed significantly more frequent "high p53 expression" and "loss of SMAD4 expression" than the PanIN-high group (p = 0.048 and p = 0.019, respectively). Loss of p16 expression was not significantly different between the groups. The rate of KRAS wild type was significantly higher in the PanIN-low group than the PanIN-high group (p = 0.024).
  
  
  CONCLUSIONS
  Our results demonstrated that the molecular characteristics in the PDACs with high-grade PanIN were different from those in the PDACs without high-grade PanIN. PDACs without high-grade PanIN may develop via a pathway other than the PanIN-carcinoma sequence.
authors.affiliation: Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohishi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyasaka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Oda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Aishima
authors.forename: Keigo
authors.initials: K
authors.lastname: Ozono
authors.forename: Atsushi
authors.initials: A
authors.lastname: Abe
authors.forename: Eishi
authors.initials: E
authors.lastname: Nagai
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D000368:Aged; D002278:Carcinoma in Situ / Q000150:complications*; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D051901:Smad4 Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C117307:KRAS protein, human; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; Pancreatic ductal adenocarcinoma; Pancreatic intraepithelial neoplasia; SMAD4; p53