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.
Highlights
Summary The association between Ki-ras mutations and proliferation activity was investigated in a comprehensive series of biliary tract carcinomas (BTCs)
In extrahepatic cholangiocarcinomas (ECCs) the highest value of 82% (9 of 11) was found for carcinomas located in the lower part of the biliary tree
Mean proliferating cell nuclear antigen (PCNA) labelling index (LI) in mutation-positive BTCs was significantly elevated compared with the mutation-negative value
Summary
Tumour materialsFormalin-fixed, paraffin-embedded tissue material from 77 BTC patients in the pathological archives of Nara Medical University and its satellite hospitals was used for the analysis. In all cases the location and origin of the tumours could be confirmed by clinical and pathological examinations and pancreatic or papilla Vater carcinomas were not included. ICCs were divided into two groups and ECCs into three groups depending on the location of the tumour origin. According to the classification of Okuda et al (1977), a peripheral ICC (n = 12) is defined as a tumour originating from the bile duct peripheral to the second fork and a hilar ICC (n = 10) is one originating from the bile duct between the second fork and the hepatic hilus. Proximal (n = 17), middle (n = 8) and distal (n = 11) ECCs are defined as tumours originating from the bile duct between the hepatic hilus and the cystic duct junction, the cystic duct junction
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