Ki-ras and p53 gene mutations in pancreatic ductal carcinoma: a relationship with tumor phenotype and survival

We investigated a series of clinically well documented pancreatic ductal ad enocarcinomas for the presence of molecular alterations of the p53 and Ki-r as genes and their correlations with p53 nuclear immunohistochemical expres sion. The results were evaluated in comparison with cellular expression, by ductal cancer cells, of gastric (PGII) and intestinal (CAR-5) antigens and with several clinicopathologic parameters such as grade, stage, size and l ymph-node status. Ki-ras gene mutation at codon 12 was detected in 77.7% of cases with no relationship with tumor grade, stage, and survival of the pa tients. p53 gene mutations were found in 18/31 (58%) cases and p53 immunohi stochemical overexpression was detected in 51/104 (49%) of cases. Both Ki-r as and p53 gene mutations were found in 13/31 (41.9%) of adenocarcinomas ex amined, while Ki-ras and p53 overexpression was detected in 19/45 (42.2%). A positive correlation between p53 overexpression and tumour grade was foun d (p0.0001) but no relationship was found between p53 overexpression, tumor stage, lymph-node status and size of the tumors. A trend toward an associa tion of p53 overexpression with poorer survival was found in patients with pancreatic cancers of the same grade, stage or with the same immunophenotyp e, but the data did not reach statistical significance. The expression of g astric and intestinal antigenic markers in pancreatic adenocarcinomas and t he presence of molecular abnormalities analogous to those found in gastric and colorectal cancers suggest common genetic pathways in gastrointestinal and pancreatic carcinogenesis.