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

Alterations of K-ras, p53, p16 and DPC4/Smad4 characterize pancreatic ducta l cancer (PDC). Reports of inactivation of these latter two genes in pancre atic endocrine tumours (PET) suggest that common molecular pathways are inv olved 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-r as 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, respectiv ely and in 47%, 60%, 25% and 6% of AVC. Alterations in these genes were vir tually absent in PET, PAC or SPT, while in IPMT only K-ras mutations were p resent (30%). Positive immunostaining confirmed the absence of DPC4 alterat ions in all IPMT, SPT PAC and PET, while 47% of PDC and 38% of AVC were imm unonegative. These data suggest that pancreatic exocrine and endocrine tumo urigenesis involves different genetic targets and that among exocrine pancr eatic neoplasms, only ductal and ampullary cancers share common molecular e vents. (C) 2001 Cancer Research Campaign.