Barrett上皮ならびにBarrett腺癌の組織学的・粘液および免疫組織化学的検討

Histological, Mucin Histochemical and Immunohistochemical Study of Barrett's Epithelium and Adenocarcinoma

要旨　外科的切除で得られたBarrett腺癌13症例14病変を含むBarrett食道22症例を用いて組織形態学的・粘液および免疫組織化学的にBarrett上皮ならびに腺癌の検討を行った．Barrett分化型腺癌を細胞異型・構造異型の点から高異型度と低異型度に分類したところ，主として早期の病変において，6病変に高異型度癌と混在した低異型度癌の成分が含まれていた．Barrett食道を構成する非癌上皮は種々の程度で胃型・腸型の組織形態・粘液形質発現を示しており，Barrett上皮が長くなるほど腸型の粘液形質を有する杯細胞の比率が有意に増加していた．しかし胃型形質を保持した上皮も保たれ，吸収上皮細胞への分化がさほど進まないことが特徴であった．Barrett腺癌の粘液形質は粘膜内では胃型優勢の胃腸混合型で，浸潤部では腸型優勢となっていた．Ki-67・p53蛋白についての免疫組織学的検討では異型度の高い上皮ほど増殖帯は粘膜深層から表層に分布し，Ki-67・p53蛋白染色陽性細胞のlabeling indexが高値となっていた．以上の結果から，Barrett腺癌の組織診断においては浸潤の有無ではなく，細胞異型・構造異型の点で評価することが重要と思われた．またBarrett腺癌は胃型の形質を有する上皮から発生し，進行とともに腸型への形質変化が起こると考えられた．

　Histological, mucin histochemical and immunohistochemical study of 22 surgically resected cases of Barrett's esophagus including 14 Barrett's adenocarcinomas was examined. Barrett's differentiated adenocarcinomas were classified as adenocarcinomas with low grade and high grade atypia from view points of structural and cellular atypia. Of the 14 lesions with Barrett's adenocarcinoma, 6 included components of adenocarcinoma with histologically mixed low and high grade atypia. The various patterns of histological feature and mucin phenotype were observed in Barrett's epithelium. With the longer Barrett's epithelium, the ratio of columnar cells containing gastric type mucins was significantly lower. On the other hand, the ratio of goblet cells containing intestinal type mucins were significantly higher. However, the differentiation to absorptive cells was not remarkable, and histological feature of Barrett's epithelium was mainly composed. of gastric foveolar epithelium with goblet cell metaplasia showing both gastric and intestinal mucin phenotypic expression. Mucin phenotype of Barrett's adenocarcinomas was predominantly gastric phenotype in the mucosa, and was significantly transformed to intestinal phenotype below the submucosal layer. Immunohistological study of Ki-67 and p53 protein showed that the increasing grade of atypia was accompanied by an upward shift of the Ki-67 proliferative compartment and an increased labeling index of Ki-67 and p53 protein positive cells. Accordingly, it is important that Barrett's adenocarcinoma should be diagnosed based on structural and cellular atypia. Our results suggest that Barrett's adenocarcinoma might arise from Barrett's epithelium containing gastric type mucins and that mucin phenotype of Barrett's adenocarcinoma might be transformed to intestinal phenotype with progression of the tumor.