微小胃癌の病理―分化型微小胃癌の臨床病理学的および分子病理学的特徴

Clinicopathological and Molecular-pathological Characteristics of Minute Gastric Adenocarcinoma

要旨　【目的】微小胃癌（5mm以下）の臨床病理学的および分子病理学的特徴の意義を明らかにするため，非微小胃癌（10mm以上）と比較検討した．【対象と方法】内視鏡的に切除された微小胃癌86例と非微小胃癌83例を対象とし，臨床病理学的事項，腫瘍グレード，背景粘膜および粘液形質について比較した．また，p53，MLH-1，β-cateninおよびKi-67について免疫組織化学的に解析した．さらに，癌および背景粘膜におけるDNAメチル化解析をLOX，MINT31，RUNX3，ELMO1，THBD，NEUROG1，SOCS1，p16，hMLH1の9遺伝子について行い，Yagiらの2パネル法に従って，DNAメチル化状態を分類した．【結果】微小胃癌では，（1）胃下部発生，（2）0-IIb型，（3）低グレード癌を示す症例が多かった．背景粘膜には両者に差はなかった．微小胃癌の粘液形質は胃型が少なく，小腸型が多かった．p53およびMLH-1発現は両者に差はなかったが，微小胃癌ではβ-cateninの核内蓄積の頻度が低かった．また，Ki-67陽性細胞の頻度と分布は両者に差はなかった．DNAメチル化では，微小胃癌は非微小胃癌と比較し，低メチル化状態の頻度が高く，高メチル化状態の頻度が低かった．背景粘膜のDNAメチル化に差はなかった．【結語】微小胃癌と非微小胃癌では，DNAメチル化の蓄積状態に差異があることが明らかとなった．

　Background and aims : Our aim is to clarify the significance of clinicopathological and molecular-pathological characteristics of minute gastric adenocarcinomas, compared with non-minute gastric adenocarcinomas. Material and methods : Eighty-six minute gastric adenocarcinomas and 83 non-minute gastric adenocarcinoma obtained by endoscopic submucosal dissection were examined. We histologically examined clinicopathological features, tumor grades, findings of back-ground mucosa and mucin phenotype, immunohistochemically. Immunohistochemical analysis for p53, MLH-1 and beta-catenin were also performed. Furthermore, DNA methylation status of cancer and back-ground mucosa were classified using nine genes（LOX, MINT31, RUNX3, ELMO1, THBD, NEUROG1, SOCS1, p16, hMLH1）according to 2 panel methods of Yagi et al. Results : In minute gastric adenocarcinoma,（1）lower gastric location,（2）IIb macroscopical finding and（3）low grade cancer, were more frequently found compared with non-minute adenocarcinoma. Although there were no significant differences in expression of p53 and MLH-1, intranuclear accumulation of beta-catenin were more frequently found in minute adenocarcinoma. There were no significant differences for positive-rate and intraglandular distribution of Ki-67 positive cells. Low DNA methylation status was frequently found in minute gastric adenocarcinoma and high DNA methylation status was less frequent in minute gastric adenocarcinoma than non-minute gastric adenocarcinoma. There were no significant differences for DNA methylation status of back-ground mucosa between minute and non-minute adenocarcinoma. Conclusions : We could clarify there are the differences in accumulation of DNA methylation between minute and non-minute gastric adenocarcinomas.