1998 Fiscal Year Final Research Report Summary
molecular biological characteristics of carcinoma of the papilla of Vater
| Project/Area Number |
08671413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | First Department of Surgery, Yamagata University School of Medicine (1998)
The University of Tokyo (1996-1997) |
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Principal Investigator |
KIMURA Wataru First Department of Surgery, Yamagata University School of Medicine, Professor, 医学部, 教授 (00169947)
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| Co-Investigator(Kenkyū-buntansha) |
KUDO Shun First Department of Surgery, Yamagata University School of Medicine, Assistant P, 医学部附属病院, 助手 (60302296)
KUZU Hiroshi First Department of Surgery, Yamagata University School of Medicine, Assistant P, 医学部附属病院, 助手 (60241717)
FUSE Akira First Department of Surgery, Yamagata University School of Medicine, Associated, 医学部附属病院, 講師 (80199398)
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| Project Period (FY) |
1996 – 1998
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| Keywords | p53 / p21 / Waf1 / K-ras codon 12 / intestinal type / pancreaticobiliary type / carcinoma / the papilla of Vater |
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| Research Abstract |
Objectives. The aim of this study is to perform molecular biological investigation of the bile for differential diagnosis of tumorous and non-tumorous lesions, and of benign and malignant lesions of the biliary tract. As the basic study of this aim, we studied on the molecular biological characteristics of carcinoma of the papilla of Vater. p53 and p21/Waf1 expression and K-ras codon 12 mutation in carcinoma of the papilla of Vater were investigated.
Methods. Thirty seven' cases of carcinoma of the papilla of Vater were studied. Macroscopically, the carcinoma was ulcerative in 15 cases and non-ulcerative in 22 cases. Histologically, nine were intestinal type, 27 were pancreaticobiliary type, and one was undifferentiated. Formalin-fixed, paraffin-embedded sections were immunohistochemically stained for p53 and p21. K-ras codon 12 mutation was detected with the two-step polymerase chain reaction-restriction fragment length polymorphism method followed by direct sequencing.
Results. p53 overexpression was found in 17 of 37 cases (46%) and was more frequent in the ulcerative type than in the non-ulcerative type (67% vs. 32%, p<0.05). p21/Wafi protein expression was found in 15 of 37 cases (41%), and was not correlated with that of p53. K-ras codon 12 mutation was found in 14 of 37 cases (38%), and was more frequently detected in the intestinal type than in the pancreaticobiliary type (66% vs. 30%, p<0.05). On direct sequencing, the mutations were mainly GGT to GAT (9/14) and GGT to GTT (4/14). The type of mutation did not correlate with the histological type.
Conclusions. In carcinoma of the papilla of Vater, p53 overexpression may play a role in tumor ulceration. p21/Waft expression is induced via a p53-independent pathway. Carcinomas of the intestinal and pancreaticobiliary types may develop via different mechanisms, and K-ras mutation is mainly associated with the intestinal type.
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