P53 AND K-RAS STATUS IN DUODENAL ADENOMAS IN FAMILIAL ADENOMATOUS POLYPOSIS

Background The genetic alterations in patients with familial adenomato us polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same p atients. Methods Point mutation of the K-ras oncogene and point mutati on and overexpression of the TP53 tumour suppressor gene were investig ated in 32 duodenal polyps (seven without mucosal pathology, 23 with m ildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. Results K-ras mutation, TP53 mutation or p ositive p53 staining were not found in duodenal polyps without histolo gical abnormality. Of 25 duodenal adenomas, K-ras mutation was found i n three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found i n one moderately dysplastic adenoma. p53 protein overexpression in duo denal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). Conclusion p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP, Overexpression may indicate D NA damage and thus an early step in tumorigenesis.