Histochemical and genetic study of cystic tumors of the pancreas

背景和目的：由于诊断成像技术的进步，胰腺囊性肿瘤越来越多地被发现。IPMT和MCT无侵袭亚分类的组织病理学标准仍然不明确，似乎因机构或病理学家而异。当在手术边缘发现发育不良的上皮时，这通常是一个问题。为了阐明这一问题，我们评估了胰腺囊性肿瘤（IPMT和MCT）的克隆性和K-ras突变。材料与方法：在23例女性IPMT或MCT患者中，11例显示x连锁磷酸甘油酸激酶基因（PGK）多态性。我们研究了用10%福尔马林固定和石蜡包埋的切除标本的档案材料。我们将不同程度的异型性分为4个等级（0-3级）。对激光显微解剖上皮细胞的DNA进行分析，显示个体肿瘤中不同程度的异型性。我们基于甲基化诱导的x染色体连锁PGK的任意等位基因的缺失来评估克隆性。采用巢式PCR对所有样品的第12个密码子进行K-ras分析。结果：0级患者单克隆发生率为27%(3/11)，单克隆发生率随非典型性分级而增加：1级为43%，2级和3级为100%。在IPMT中，5例在0年级表现为多克隆的患者在非典型年级获得了单克隆。在mct中，只有1个（25%）0级位点显示单克隆，而其他3个（75%）显示多克隆。K-ras突变和克隆性随非典型性程度的增加而增加；1年级为29%，2年级为50%，3年级为75%，而0年级没有K-ras突变。突变模式在所有四个ipmt中都是不同的。在MCT中，即使在密码子12处也没有K-ras突变的病例。结论:1。在ipmt中，单克隆的发生率随着非典型性的分级而增加。MCT的多克隆0级暗示非肿瘤性，未证明与ipmt有差异。克隆分析表明，单克隆扩增先于K-ras突变。少

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