胃腺腫と腫瘍グレードに基づいた分化型粘膜内胃癌の臨床病理学的および分子病理学的解析

Clinico-pathological and Molecular Alterations of Gastric Adenomas and Gastric Intramucosal Differentiated-type Cancer Based on Tumor Grade

要旨　目的：腺腫と分化型粘膜内胃癌（低グレード，中等度グレード，高グレードに分類）の臨床病理学的，分子病理学的特徴を解析した．材料と方法：腺腫8例と分化型胃粘膜内癌83例を対象にした（低グレード癌26例，中等度グレード癌44例，高グレード癌13例）．LOHおよびMSIはPCR-microsatellite法により，メチル化はCOBRA法で解析した．LOHは，5q，17p，18q，3p，4pについて行った．メチル化の解析は，p16，MLH-1，RUNX3，RASSF2A，DKK-1，SFRP1，の各遺伝子について施行した．加えてp53，ki-67，catenin，MLH1の発現の解析も免疫組織化学的に行った．結果：腺腫群，低グレード癌群ではLOH率およびp53過剰発現には差異はみられなかったが，高グレード癌群では両者ともそれらの頻度が高かった．中等度異型度癌群は中間的なパターンであった．一方メチル化率は，いずれのグループでも比較的高頻度であった．結語：腺腫，低グレード癌は，分子異常の観点からは，同一のカテゴリーに属する腫瘍群であることが示唆された．

　Background and aims : Our aim was to identify clinicopathological findings and molecular alterations in gastric adenoma and gastric intramucosal differentiated-type cancers that are classified into three groups based on their tumor grades（low, intermediate and high grade）. Materials and methods : Eighty-three gastric intramucosal differentiated-type cancers consisting of 26 low-grade, 44 intermediate grade, and 13 high-grade tumors and 8 gastric adenomas were examined. Tumors were examined for immunohistochemical expression of p53, ki-67, -catenin, and ki-67 and MLH-1 for genetic alterations, including loss of heterozygosity（LOH）in chromosome arms 3p, 4p, 5q, 17p, and 18q ; MSI ; and DNA methylation status of a panel of 6 genes（,,,, and ）. Results : LOHs for examined markers are frequently found in high grade cancers, compared with gastric adenomas and low grade cancers. On the other hand, methylated level for examined genes is common in gastric adenomas and gastric intramucosal cancers. However, no differences between gastric adenomas and low grade cancers were observed. Conclusions : Our results suggest that gastric adenoma and low grade cancers share common molecular alterations.