Abstract
Periampullary carcinomas are a group of rare lesions around the ampulla of Vater including distal bile duct and duodenum and are very different from pancreatic ductal adenocarcinoma clinically and pathologically, but the molecular alterations in these tumours are less known. Genetic alterations of the KRAS oncogenes, tumour suppressor genes p53, p16 and MADH4 (SMAD4/DPC4) and genome maintenance genes (MLHI, MSH2) are commonly altered in pancreatic adenocarcinoma and have also been described in periampullary cancers, although at lower frequencies. To understand the molecular characteristics of non-pancreatic periampullary carcinomas, ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. KRAS mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42-52%), biliary (22-23%) and duodenal cancers (32-35%). Mutations are also found in tumour suppressor genes (p53) and are associated with transformation of adenomas and low-grade carcinomas into high-grade carcinomas. Loss of DPC4 occurs late in ampullary carcinogenesis. This study summarizes the current knowledge in molecular aberrations in non-pancreatic periampullary cancers.