Zhang F, Chen X-P, Zhang W, Dong H-H, Xiang S, Zhang W-G, Zhang B-X
Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Histopathology. 2008 Jan;52(2):224-32. doi: 10.1111/j.1365-2559.2007.02929.x.
Combined hepatocellular cholangiocarcinoma (CHC) is a rare form of primary liver cancer, showing a mixture of hepatocellular and biliary features. Data suggest that most CHC arise from hepatic progenitor cells (HPCs). The aim was to investigate the origin of CHC.
Twelve cases of CHC were studied by immunohistochemistry for hepatocytic (hepPar1, alpha-fetoprotein), cholangiocytic cytokeratin [(CK) 7, CK19], hepatic progenitor cell (OV-6), haematopoietic stem cell (c-kit, CD34), as well as CD45 and chromogranin-A markers. The combination of double-fluorescence immunostaining consisted of HepPar1 with CK19, and c-kit with OV-6. All 12 cases demonstrated more or less transitional areas, with strands/trabeculae of small, uniform, oval-shaped cells including scant cytoplasm and hyperchromatic nuclei embedded within a thick, desmoplastic stroma; however, two cases were found to consist entirely of such transitional areas. Simultaneous co-expression of hepPar1 and CK7, or CK19, was demonstrated in 10/12 (83.3%) cases of CHC. c-kit expression was noted in 10/12 (83.3%) cases, of which 7/10 (70%) showed co-expression of OV-6.
The results suggest that CHC are of HPC origin, supporting the concept that human hepatocarcinogenesis may originate from the transformation of HPCs.
肝内胆管癌（CHC）是原发性肝癌的一种罕见形式，具有肝细胞和胆管细胞特征的混合表现。数据表明，大多数CHC起源于肝祖细胞（HPC）。本研究旨在探讨CHC的起源。
对12例CHC病例进行免疫组化研究，检测肝细胞标志物（hepPar1、甲胎蛋白）、胆管细胞细胞角蛋白（CK）7、CK19、肝祖细胞标志物（OV-6）、造血干细胞标志物（c-kit、CD34）以及CD45和嗜铬粒蛋白A。双重荧光免疫染色组合包括HepPar1与CK19、c-kit与OV-6。所有12例病例均或多或少存在移行区，有小的、形态一致的椭圆形细胞条索/小梁，胞质稀少，核深染，包埋于致密的促纤维组织增生性间质中；然而，发现2例完全由这种移行区组成。12例CHC病例中有10例（83.3%）同时出现hepPar1和CK7或CK19的共表达。12例病例中有10例（83.3%）出现c-kit表达，其中10例中有7例（70%）出现OV-6的共表达。
结果表明，CHC起源于HPC，支持人类肝癌发生可能起源于HPC转化的观点。
