Abstract
Expression of p 53 protein products and p 53 gene mutations in biliary duct carcinomas were examined to evaluate the relationship between p 53 gene mutation and the clinicopathological factors. The expression of p 53 protein products was examined by an immunohistochemical staining using a monoclonal antibody against p 53 protein. p 53 gene mutations in exon 5,6,7 and 8 were examined by the PCR-SSCP method and the direct sequencing method. Positive rate of the expression of p 53 protein was 100% in intrahepatic cholangiocarcinomas and 29.2% in extrahepatic bile duct carcinomas, respectively. Positive rate of p 53 gene mutations was 100% in intrahepatic cholangiocarcinomas and 62.5% in extrahepatic bile duct carcinomas, respectively. p 53 gene mutations were detected in exon 5,7, and 8, whereas no mutation was detected in exon 6. By direct sequencing method, the point mutations were detected in 18 out of 24 cases and totally 26 point mutations was noted in these cases. In one case, deletion type of mutation was noted, and in others, they were point mutations. Multiple gene mutations were noted in 38.9% (7/18) of the cases. The transversion type of the point mutation was seen in 23.1%, whereas transition type was seen in 76.9%. Because transversion type of point mutation has been reported that they were frequently seen in the circumstance under an exposure of carcinogenic substances, the presence of transversion type of point mutation in such cases with biliary duct carcinoma suggested that they might be affected by some carcinogenic substances. These results of the present study may suggest that the mutations of p 53 gene play an important role in biliary duct carcinogenesis, but also we must consider that other gene groups may also play some roles in carcinogenic process.
