Histochemical and genetic study of cystic tumors of the pancreas

背景和目的：由于影像诊断技术的进步，胰腺囊性肿瘤的检出率越来越高。IPMT和无侵袭性MCT的亚分类的组织学标准仍然不明确，并且似乎因机构或病理学家而异。当在手术切缘发现发育不良的上皮细胞时，这通常是一个问题。为了阐明这一问题，我们评估了克隆性和K-ras突变在胰腺囊性肿瘤（IPMT和MCT）。材料和方法：在23例女性患者与IPMT或MCT，11例显示信息多态性的X-连锁磷酸甘油酸激酶基因（PGK）。我们调查档案材料的切除标本固定在10%福尔马林和石蜡包埋。我们将不同程度的痴呆分为4级（0 -3级）。对来自激光显微切割的上皮细胞的DNA进行分析，显示个体肿瘤中不同程度的凋亡。我们根据甲基化诱导的失活来评估克隆性。 关于我们 X染色体连锁PGK的任一等位基因的产生。结果：0级患者中有27%（3/11）的患者存在单克隆性，且单克隆性的发生率随疾病级别的增加而增加，1级患者为43%，2、3级患者为100%。在IPMT中，5例在0级时显示多克隆性的病例在非典型级时获得单克隆性。在MCT中，只有1个（25%）0级站点显示单克隆性，而其他3个（75%）显示多克隆性。K-ras基因突变和克隆性随宫颈癌的分级而增加，1级为29%，2级为50%，3级为75%，0级无K-ras基因突变。四种IPMT的突变模式不同。MCT中K-ras基因第12位密码子未发生突变。单克隆发生率随IPMT患者病情分级的增加而增加. MCT中多克隆0级意味着非肿瘤性，与IPMT无明显差异。克隆性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