Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis

Br J Cancer. 2001 Jan;84(2):253-62. doi: 10.1054/bjoc.2000.1567.

Abstract

Alterations of K- ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPMT), 6 acinar carcinomas (PAC), 5 solid-pseudopapillary tumours (SPT), 16 ampulla of Vater cancers (AVC) and 41 PET. All tumours were also presently or previously analysed for K- ras and p53 mutations and allelic loss at 9p, 17p and 18q. Alterations in K- ras, p53, p16 and DPC4 were found in 82%, 53%, 38% and 9% of PDC, respectively and in 47%, 60%, 25% and 6% of AVC. Alterations in these genes were virtually absent in PET, PAC or SPT, while in IPMT only K- ras mutations were present (30%). Positive immunostaining confirmed the absence of DPC4 alterations in all IPMT, SPT, PAC and PET, while 47% of PDC and 38% of AVC were immunonegative. These data suggest that pancreatic exocrine and endocrine tumourigenesis involves different genetic targets and that among exocrine pancreatic neoplasms, only ductal and ampullary cancers share common molecular events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Ampulla of Vater / metabolism
  • Ampulla of Vater / pathology
  • Base Sequence
  • Carcinoma, Acinar Cell / genetics
  • Carcinoma, Acinar Cell / metabolism
  • Carcinoma, Acinar Cell / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology
  • Common Bile Duct Neoplasms / genetics
  • Common Bile Duct Neoplasms / metabolism
  • Common Bile Duct Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • Endocrine Gland Neoplasms / genetics
  • Endocrine Gland Neoplasms / metabolism
  • Endocrine Gland Neoplasms / pathology
  • Endocrine Glands / metabolism
  • Endocrine Glands / pathology
  • Exocrine Glands / metabolism
  • Exocrine Glands / pathology
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • Mutation
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Polymorphism, Single-Stranded Conformational
  • Smad4 Protein
  • Trans-Activators / analysis
  • Trans-Activators / genetics
  • Tumor Suppressor Protein p53 / analysis
  • Tumor Suppressor Protein p53 / genetics
  • ras Proteins / analysis
  • ras Proteins / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA-Binding Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • DNA
  • ras Proteins