肝硬化组织中卵圆细胞的光镜、电镜与免疫电镜观察

Oval cells in liver cirrhosis: histologic, electron microscopic and immunoelectron microscopic findings

目的 :探讨人肝硬化肝组织是否存在卵圆细胞。方法 :对 30例人肝细胞肝癌手术标本的癌旁肝硬化组织行常规组织学观察 ,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 10例作了超微结构观察 ,5例作免疫电镜标记和观察。另外对 5例正常肝脏和 5例肝炎后肝硬化组织同时作了光镜、免疫组化和电镜观察 ,对 2例肝炎后肝硬化作了免疫电镜标记和观察。结果 :癌旁肝硬化组织的 30例光镜和 10例电镜观察以及 5例肝炎肝硬化光、电镜观察 ,均可在再生的肝细胞结节边缘见到散在的小细胞和增生的小胆管样结构。这些小细胞和增生的小胆管内少数小细胞 ,为卵圆形 ,体积较小 ,核大 ,胞质少 ,胞质内含较多的游离核糖体 ,仅含少量粗面内质网和线粒体 ,胞质内可见张力微丝结构 ,这类细胞与邻近细胞间均有细胞间连接。免疫电镜示 ,卵圆细胞均表达CK7和白蛋白 ,但有些细胞内表达CK7多些 ,有些细胞则表达白蛋白多些。在正常肝组织内未见到类似细胞。结论 :与动物实验性肝癌模型肝组织一样 ,人类肝硬化肝组织中也存在同样细胞形态和免疫表型特点的卵圆细胞。

Purpose To investigate whether oval cells occur in human liver cirrhosis (HLC). Methods Surgical specimens from 30 cases of HLC adjacent to human hepatocellular carcinoma (HCC) were investigated by light microscopy and immunohistochemical staining for cytokeratin 7 (a marker of biliary differentiation in the liver) and albumin (a marker of hepatocytic differentiation). 10 cases were investigated by electron microscopy. Double labeling with both antibodies was carried out by immunoelectron microscopy in 5 cases. As a control, 5 cases of normal liver and 5 hepatitis cirrhosis were observed. Results Proliferating bile ductules and scattered small cells were seen in fibrous septae and at the margins of regenerating nodules in all 30 cases light microscopically, in 10 cases of HLC adjacent to HCC electron microscopically and in 5 cases of hepatitis cirrhosis light and electron microscopically. Some of the cells in the proliferating bile ductules and the scattered small cells were morphologically similar to the small epithelial cells described previously in hepatoblastoma, biliary atresia, HCC, and to the oval cells seen in experimental hepatocarcinogenesis. These cells were characterized by their small size, oval shape (hence their designation as 'oval cells'), scanty electron dense or electron lucent cytoplasm, a high nucleocytoplasmic ratio, tonofilament bundles and intercellular junctions. Immunoelectron microscopy revealed that the oval cells coexpressed cytokeratin 7 and albumin. Relatively undifferentiated oval cells and oval cells that exhibited morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes were found. The similar cells were not found in 5 cases of normal liver. Conclusions Oval cells that exhibit the same morphologic and immunophenotypic features as those seen during hepatocarcinogenesis in animals are found in HLC. The findings support the hypothesis that these oval cells are possible candidates for hepatic progenitor cells.