Histochemical and genetic study of cystic tumors of the pancreas

胰腺囊性肿瘤的组织化学和遗传学研究

基本信息

批准号：
12671254
负责人：
NAGAI Hideo
金额：
$ 1.79万
依托单位：
JICHI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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 … More 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

背景和目的：由于诊断成像技术的进步，无侵袭性 IPMT 和 MCT 亚分类的组织病理学标准仍然不明确，并且似乎因机构或病理学家而异，这通常是发育不良上皮的问题。为了阐明这个问题，我们评估了胰腺囊性肿瘤（IPMT 和 MCT）的克隆性和 K-ras 突变。材料和方法： 23 名患有 IPMT 或 MCT 的女性患者，其中 11 名显示 X 连锁磷酸甘油酸激酶基因 (PGK) 的信息多态性。我们研究了固定在 10% 福尔马林并包埋在石蜡中的切除标本的档案材料，我们将不同程度的异型性分为 4 级。（0-3 级）。对激光显微切割上皮细胞的 DNA 进行分析，显示个体肿瘤中不同程度的异型性。所有样本中 X 染色体连锁 PGK 的任一等位基因的甲基化诱导的非活性激活均采用巢式 PCR 进行，密码子 12 处的 K-ras 分析结果：Grade0 具有 27% (3/11) 的单克隆性，并且单克隆性的发生率随着异型性等级的增加而增加：1级为43%，2级和3级为100%。在IPMT中，5例在 MCT 中，只有 1 个（25%）0 级位点表现出单克隆性，而其他 3 个（75%）则表明 K-ras 突变以及克隆性随着异型性等级的增加而增加。 1 级为 %，2 级为 50%，3 级为 75%，而 0 级没有 K-ras 突变。所有四种IPMT中，即使在密码子12处也没有K-ras突变的病例。结论：1. MCT中的多克隆0级是非肿瘤性的。未证明与 IPMT.3 的差异。克隆性分析表明单克隆扩增先于 K-ras 突变。