MOLECULAR PATHOGENESIS OF SPORADIC DUODENAL CANCER

Whether duodenal adenocarcinoma should be considered as a gastrointest inal or as a peripancreatic cancer is a matter of debate, as is the op portunity and type of treatment. We investigated 12 such cancers for t he genetic anomalies involved in the pathogenesis of gastrointestinal malignancies, including (a) those occurring in common-type cancers - a llelic losses at chromosomes 3p, 5q, 17p and 18q, and Ki-ras and p53 a lterations; and (b) those characteristic of mutator-phenotype cancers - microsatellite instability and TGF-beta RII gene mutations. We found Ki-ras and p53 mutations in five (42%) and eight cancers (67%), respe ctively; chromosome 3p, 5q, 17p and 18q allelic losses in two of nine (22%), six of ten (60%), six of nine (67%) and three of ten (30%) info rmative cancers, respectively. Finally, three cancers (25%) showed wid espread microsatellite instability and two of them had a TGF-beta RII gene mutation. Our data suggest that duodenal cancers may arise from e ither of the two known pathogenetic molecular pathways of gastric and colorectal cancers. The majority of our cases were highly aggressive c ancers with frequent chromosomal changes and p53 mutations as observed in the common-type gastrointestinal malignancies, while widespread su btle alterations characteristic of mutator-phenotype cancers occurred in a minority, which also showed a favourable long-term outcome.