| Project/Area Number |
12671254
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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 | JICHI MEDICAL SCHOOL |
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Principal Investigator |
NAGAI Hideo Jichi Medical School of Medicine, professor, 医学部, 教授 (00164385)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Katsumi Jichi Medical School of Medicine, assitant professor, 医学部, 講師 (20275697)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | pancreas / IPMT / MCT / clonality / X chromosome inactivation / PGK / K-ras / 膵嚢胞 / 嚢胞性膵腫瘍 / 組織学的異型度 / マイクロダイセクション / クロナリティ解析 |
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| Research Abstract |
Background and aims : Cystic tumors of the pancreas have increasingly been detected due to advances in diagnostic imaging technology. Histopathological criteria for subclassification of IPMT and MCT without invasion remain ambiguous and seem to differ by institution or pathologist. This is often a problem when dysplastic epithelia are seen at the surgical margin. To elucidate this issue, we evaluated clonality and K-ras mutations in cystic tumors of the pancreas(IPMT and MCT).
Material and methods : Among the 23 female patients with IPMT or MCT, 11 showed informative polymorphism of the X-linked phosphoglycerate kinase gene (PGK). We investigated archival materials of resected specimens fixed in 10% formalin and embedded in paraffin. We classified various degrees of atypia into 4 grades(grade0-3). The analyses were performed on DNA from laser microdissected epithelia showing different degrees of atypia in the individual tumors. We evaluated clonality based upon methylation-induced inact
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ivation of either allele of X-chromosome-linked PGK. K-ras analyses at codons 12 in all samples were performed with nested PCR.
Results : Grade0 had monoclonality in 27% (3/11), and the incidence of monoclonality increased with the grades of atypia : 43% for grade 1 and100% for grades 2 and 3. In IPMT, 5 cases that showed polyclonality in grade0 acquired monoclonality at atypical grades. In MCTs, only 1 (25%) grade0 site showed monoclonality whereas the other 3 (75%) indicated polyclonality. K-ras mutation as well as clonality increased with grades of atypia ; 29% for grade 1, 50% for grade 2, and 75% for grade 3, whereas grade0 had no K-ras mutation. The mutation patterns were different in all four IPMTs. In MCT, there were no cases of K-ras mutation even at codon 12.
Conclusions :
1. The incidence of monoclonality increased with the grades of atypia in IPMT.
2. Polyclonal grade0 in MCT was implied non-neoplastic, not proved differences from IPMT.
3. Clonality analysis suggests that the monoclonal expansion precedes K-ras mutation. Less
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