KI-RAS MUTATIONS AND P53 PROTEIN EXPRESSIONS IN INTRAHEPATIC CHOLANGIOCARCINOMAS - RELATION TO GROSS TUMOR MORPHOLOGY

Background & Aims: We previously reported that intrahepatic cholangioc arcinomas (ICCs) can be divided into three categories according to the ir gross appearance with possible links to biological behavior. Ki-ras and p53 gene alterations are thought to be involved in early and late phases of carcinogenesis, respectively. This study was performed to i nvestigate the relationship between the gross appearance and genetic a lterations of ICC. Methods: We examined 21 patients with ICC. Ki-ras p oint mutations were assessed by polymerase chain reaction/single-stran d conformation polymorphism methods followed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. Resul ts: Ki-ras point mutations were found in 10 patients (48%), and expres sions of p53 protein were detected in 4 (19%). Applying the gross clas sification that we previously proposed, Ki-ras mutations were prominen t in the periductal extension type (4 of 6; 67%) and the spicula-formi ng type (6 of 10; 60%). On the other hand, none of the five mass-formi ng-type tumors harbored Ki-ras mutations. Expressions of p53 protein d id not show any clear association with gross appearance. Conclusions: Ki-ras gene alterations may be involved in the cholangiocarcinogenesis of periductal extension and spicula-forming but not mass-forming type s, suggesting that the underlying processes of development are differe nt.