High rates of Ki-ras point mutation in both intra- and extra-hepatic cholangiocarcinomas.

The presence of the Ki-ras gene mutations in 14 cases of intrahepatic cholangiocarcinoma (IHC) and nine cases of extrahepatic cholangiocarcinoma (EHC) were investigated by polymerase chain reaction-single strand conformation polymorphism analysis. To obtain enriched tumor cell DNA, the microdissection method was used on formalin-fixed paraffin-embedded tissue sections. Point mutations at codon 12 of the Ki-ras gene were detected in seven (50%) of the 14 cases of IHC and six (67%) of the nine EHC cases. In all but one of the ras gene mutation cases, G to A transitions in the second position of codon 12 were detected, the exception being a G to T transition in the same position in one IHC. No point mutations were detected at codon 13 or 61 in either IHC or EHC. Furthermore, there was no demonstrable correlation between Ki-ras mutation and patient age, tumor Stage, histological findings or prognosis. The present results demonstrated a higher participation of Ki-ras gene mutations in EHC than found in previous studies, and provided a confirmation and extension of the results earlier reported by Tada et al. and Tsuda et al. for IHC.