肝细胞肝癌中卵圆细胞的组织学与超微结构研究

Oval cells in hepatocellular carcinoma: a histological and ultrastructural study

目的 :探讨人肝癌肝组织存在卵圆细胞的可能性。方法 :对 2 0例人肝细胞肝癌的手术标本行常规组织学和超微结构观察 ,并用胆管上皮分化标记CK7和肝细胞分化标记白蛋白对以上组织作免疫组化染色 ,同时对其中 5例作免疫电镜标记。结果 :光镜下 ,14/ 2 0例癌肿边缘常可见到增生的小胆管样结构。电镜下 ,14/ 2 0例可找到三型卵圆细胞。其中Ⅰ型细胞体积较小、核大、胞质少 ,此为较为原始的卵圆细胞。Ⅱ型细胞体积稍大 ,胞质稍多 ,此为向胆管上皮分化的小上皮细胞。Ⅲ型细胞体积稍大 ,内含稍多粗面内质网 ,此为向肝细胞分化的卵圆细胞。此三型卵圆细胞均有细胞内张力微丝和细胞间连接结构。免疫电镜显示 ,三型卵圆细胞均表达CK7和白蛋白 ,但Ⅰ型和Ⅱ型表达CK7多些 ,Ⅲ型表达白蛋白多些。结论 :与动物致癌模型肝中存在卵圆细胞一样 ,人肝细胞肝癌肝中也存在同样形态和免疫表型特点的卵圆细胞。结果支持卵圆细胞可能为肝前体细胞的假设。

Purpose To investigate whether the oval cells exist in human hepatocellular carcinoma (HCC). Methods Surgical specimens from 20 cases of human HCC were investigated by light microscopy, electron microscopy, and immunostaining for cytokeratin 7 (a marker of biliary differentiation), and albumin (a marker of hepatocytic differentiation). Double labeling for these two antigens was carried out by immunoelectron microscopy in 5 cases. Results Proliferating bile ductules were noted around the edges of tumors in 14 of 20 cases. Electron microscopy revealed three types of oval cells. Type Ⅰ cells were small, primitive oval cells with a high nucleocytoplasmic ratio. Type Ⅱ cells, which exhibited differentiation towards biliary epithelial cells, were larger and exhibited more cytoplasm. Type Ⅲ cells exhibited similarities with hepatocytes,which were larger and contained more rough endoplasmic reticulum. Intracellular tonofilaments and intercellular junctions were seen in all three types of oval cells. By immunoelectron microscopy all three types of oval cells were found to express cytokeratin 7 and albumin, although labeling for cytokeratin 7 was stronger in types Ⅰ and Ⅱ, and labeling for albumin was stronger in type Ⅲ. Conclusion Oval cells that exhibit the same morphologic and immunophenotypic features as those seen during animal hepatocarcinogenesis are found in human HCC. The findings support the hypothesis that oval cells are hepatic progenitor cells.