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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671254/
• 关键词: 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

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，越来越多地发现胰腺囊性肿瘤。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。当在手术边缘看到发育不良上皮时，这通常是一个问题。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：在 23 名患有 IPMT 或 MCT 的女性患者中，11 名显示出 X 连锁磷酸甘油酸激酶基因（PGK）的信息多态性。我们研究了用 10% 福尔马林固定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，显示单个肿瘤中存在不同程度的异型性。我们根据 X 染色体连接的 PGK 任一等位基因的甲基化诱导的无活性激活来评估克隆性。所有样本的第 12 号密码子均采用巢式 PCR 进行 K-ras 分析。 结果：0 级单克隆性占 27%（3/11），单克隆性的发生率随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 0 级中表现出多克隆性的病例在非典型性等级中获得了单克隆性。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%）则表现出多克隆性。 K-ras 突变和克隆性随着异型性程度的增加而增加； 1 级为 29%，2 级为 50%，3 级为 75%，而 0 级没有 K-ras 突变。所有四个 IPMT 的突变模式都不同。在MCT中，即使在密码子12处，也没有出现K-ras突变的病例。结论： 1． IPMT.2中单克隆性的发生率随着异型性等级的增加而增加。 MCT 中的多克隆 0 级暗示非肿瘤性，未证明与 IPMT.3 存在差异。克隆性分析表明单克隆扩增先于 K-ras 突变。较少的

项目成果

永井秀雄 他: "膵横断切除術"手術. 54(1). 35-41 (2000)

Hideo Nagai 等：“横切胰腺切除术”54(1) (2000)。

Katsumi Kurihara 他: "Pleomorphic Carcinoma of the Pancreas with massive Lymphocytic Stromal Infiltration and bng-Term Survival Alter Resection. A case of Lymphoepitherioma-Like carcinoma"Int J pancreatol. 27. 241-248 (2000)

Katsumi Kurihara 等人：“伴有大量淋巴细胞间质浸润和切除后的晚期生存的胰腺多形性癌。淋巴上皮瘤样癌的病例” Int J pancreatol. 27. 241-248 (2000)

Katsumi Kurihara 他: "Biliopancreatic Fistula Associated with Intraductal Papillary-Mucinous Pancreatic Cancer : Institutional Experience and Review of the Literature"Hapato-Gastroenterology. 47. 1164-1167 (2000)

Katsumi Kurihara 等人：“与导管内乳头状粘液性胰腺癌相关的胆胰瘘：机构经验和文献综述”Hapato-Gastroenterology 47. 1164-1167 (2000)。

Hyodo M 他: "Pancreatogastrostomy (PG) after pancreatoduodenectomy with or without duct-to mucosa anastomos is for the small pancreatic duct ; short-and long-term results"Hepato-gastroenterology. 47. 138-1141 (2000)

Hyodo M 等人：“胰十二指肠切除术后胰胃造口术（PG）适用于小胰管，有或无导管粘膜吻合术；短期和长期结果”Hepato-gastroenterology 47. 138-1141 (2000)。

Hyodo M 他: "Pancreatogastrostomy(PG)after pancreatoduodenectomy with or without duct-to mucosa anastomosis for the small pancreatic duct ; short-and long-term results"Hepato-gastroenterology. 47. 1138-1141 (2000)

Hyodo M 等人：“胰十二指肠切除术后胰胃造口术 (PG)，伴或不伴小胰管粘膜吻合术；短期和长期结果”《肝胃肠病学》47. 1138-1141 (2000)。