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

Background & Aims: We previously reported that intrahepatic cholangiocarcinomas (ICCs) can be divided into three categories according to their 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 investigate the relationship between the gross appearance and genetic alterations of ICC. Methods: We examined 21 patients with ICC. Ki-ras point mutations were assessed by polymerase chain reaction/single-strand conformation polymorphism methods followed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. Results: Ki-ras point mutations were found in 10 patients (48%), and expressions of p53 protein were detected in 4 (19%). Applying the gross classification that we previously proposed, Ki-ras mutations were prominent in the periductal extension type (4 of 6; 67%) and the spicula-forming type (6 of 10; 60%). On the other hand, none of the five mass-forming-type tumors harbored Ki-ras mutations. Expressions of p53 protein did 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 types, suggesting that the underlying processes of development are different.