目的混合型肝癌同时具有肝细胞癌和胆管细胞癌的成分和特征,是较为少见的肝脏上皮性恶性肿瘤。研究肝脏祖细胞标志物在混合型肝癌中的免疫表型特征,以进一步了解混合型肝癌的细胞起源和发病机理。方法采用免疫组织化学和激光共聚焦免疫荧光双标染色研究HepParl,AFP,CK19,OV-6和c-kit在12例手术切除混合型肝癌标本组织中的表达。结果12例混合型肝癌均表达HepParl、CK19和OV-6,其中8例(8/12,66.7%)的移行区域肿瘤细胞共表达HepParl/CKl9,10例(10/12,83.3%)表达c-kit,其中7例(7/10,70%)共表达OV-6/c-kit。而作为对照的单纯肝细胞癌和肝内胆管细胞癌组织中免疫荧光双标染色均为阴性。结论混合型肝癌具有肝脏祖细胞的免疫表型特征,可能起源于肝脏祖细胞的恶性转化。
Objective Comnbined hepatocellular cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. The available data suggest that most combined hepatocellular cholangiocarcinoma arise from hepatic progenitor cells which retain the potential to differentiate into the hepatocytic and biliary lineages. This study was to investigate the origine and pathogenesis of combined hepatocellular cholangiocarcinoma. Methods Specimens from 12 cases of combined hepatocellular cholangiocarcinoma were studied and immunohistochemical and confocal doublefluorescence immunostaining were performed using hepatocytic markers (HepParl, AFP), cholangiocytic marker (CK19), hepatic progenitor cells marker (OV-6), and hematopoietic stem cell marker (c-kit). The combinations of double-fluorescence immunostaining consisted of HepParl with CK19, and OV-6 with c-kit. Results Transitional areas consisted of strands/trabeculae of small, uniform, oval shaped cells with scanty cytoplasm and hyperchromatic nuclei embedded within a thick desmoplastic stroma could be seen in all cases. Among these, there were 2 specimens consisting completely of such transitional areas and thus identified as transitional type of CHC. Simultaneous co-expression of HepParl with CK19 was detected in 10/12 (83.3%) cases, c-kit expression was noted in 10/12 (83.3%) cases, in which 7/10 (70%) cases co-expressioned OV-6. Conclusions We suggest that combined hepatocellular cholangiocarcinoma are of hepatic progenitor cells origin, supporting the concepts that human hepatocarcinoma originates from the transformation of hepatic progenitor cells.