title: Ki-ras point mutations and proliferation activity in biliary tract carcinomas.
abstract: The association between Ki-ras mutations and proliferation activity was investigated in a comprehensive series of biliary tract carcinomas (BTCs). We precisely microdissected samples of tissue from paraffin-embedded sections of 77 BTCs including 22 intrahepatic cholangiocarcinomas (ICCs), 36 extrahepatic cholangiocarcinomas (ECCs), and 19 gall bladder carcinomas (GBCs). Ki-ras mutations at exons 1 and 2 were determined by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method and confirmed by direct sequencing. Proliferation activity was immunohistochemically assessed to generate proliferating cell nuclear antigen labelling indices (PCNA LIs). Ki-ras mutations were detected in 10 of 22 ICCs (45%), 24 of 36 ECCs (67%), and in 16 of 19 GBCs (84%). The frequency of Ki-ras mutations in peripheral type ICCs was 33% (4 of 12) and that in the hilar type ICCs was 60% (6 of 10). In ECCs the highest value of 82% (9 of 11) was found for carcinomas located in the lower part of the biliary tree. Mean PCNA LI in mutation-positive BTCs was significantly elevated compared with the mutation-negative value. These results indicate frequent involvement of Ki-ras mutations in BTCs, especially in GBCs and in distal ECCs, and that carcinomas harbouring a mutation feature high cell proliferation activity.
authors.affiliation: First Department of Surgery, Nara Medical University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: M
authors.initials: M
authors.lastname: Tstsumi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakajima
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000473:pathology; D002455:Cell Division; D011905:Genes, ras; D006801:Humans; D017354:Point Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
chemical_list: D018809:Proliferating Cell Nuclear Antigen