1995 Fiscal Year Final Research Report Summary
Molecular genetic analysis of the development of carcinoma of the biliary tract
| Project/Area Number |
06454380
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Mie University |
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Principal Investigator |
OGURA Yoshifumi Mie Univ.School of Medicine, 1st Dep.of Surgery Associate Professor, 医学部, 助教授 (00126963)
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| Co-Investigator(Kenkyū-buntansha) |
TAOKA Hiroki Mie Univ.School of Medicine, 1st Dept.of Surgery Assistant, 医学部, 助手 (20263006)
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| Project Period (FY) |
1994 – 1995
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| Keywords | cholangiocellular carcinoma / carcinoma of the gallbladder / nuclear DNA ploidy pattern / K-ras oncogene / p53 suppressor gene / chromosomal deletion / MIB-1-labeling index |
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| Research Abstract |
The molecular genetic and biological characteristics of carcinoma of the biliary tract were analyzed and the following results were obtained.
1.Cholangiocellular carcinoma : Although cholangiocellular carcinoma arises from the bile duct epitelium similarly to carcinoma of the hepatic duct confluence, it grows rapidly with extremely poor prognosis in contrast with carcinoma of the hepatic duct confluence. Among various molecular biological factors, the expression of p53 suppressor gene and nuclear DNA ploidy pattern showed a significant difference between these two carcinomas. The incidence of p53-positive or aneuploid tumors was significantly higher in cholangiocellular carcinoma than in carcinoma of the hepatic duct confluence, indicating that the former has a stronger cell proliferative activity than the latter. We also examined the chromosomal deletion in 7 patients with advanced cholangiocellular carcinoma and found deletion of genes on chromosome 17p in all of them. Furthermore, al
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l 6 patients who showed deletion on chromosome 16q died of tumor recurrence within 3 years, but 1 patient who had no deletion on 16q survived without recurrence for 5 yerars. Therefore, the abnormalities of choromosomes 16p and 17p are considered to be related to the occurrence and development of cholangiocellular carcinoma.
2.Carcinoma of the gallbladder : We reviewed 34 patients with early carcinoma of the gallbladder and compared various molecular biological factors with advanced cases. About 20% of patients with early carcinoma showed a high cell proliferative activity with an MIB-1-labeling index of 30% or above, and p53 was positive in 30% of them. We intend to examine differences in the molecular biological characteristics between early carcinomas that progress into advanced stages and those that remain in early stages. Various histopathological and molecular biological factors and its clinical singnificance were also examined in advanced carcinoma of the gallbladder. All patients who survived more than 3 yers after resection had no lymph node metastasis, showed a diploid type, and were negative for K-ras oncogene. Since lymph node metastasis and nuclear DNA ploidy pattern can be evaluated by intraoperative frozen spections, we have formulated a protocol for selection of surgical procedures and are collecting cases. Less
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