Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence
Article first published online: 20 DEC 2007
Volume 52, Issue 2, pages 224–232, January 2008
How to Cite
Zhang, F., Chen, X.-P., Zhang, W., Dong, H.-H., Xiang, S., Zhang, W.-G. and Zhang, B.-X. (2008), Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology, 52: 224–232. doi: 10.1111/j.1365-2559.2007.02929.x
- Issue published online: 20 DEC 2007
- Article first published online: 20 DEC 2007
- Date of submission 25 April 2007 Accepted for publication 20 August 2007
- combined hepatocellular cholangiocarcinoma;
- hepatic progenitor cells;
Aims: 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.
Methods and results: Twelve cases of CHC were studied by immunohistochemistry for hepatocytic (hepPar1, α-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.
Conclusions: The results suggest that CHC are of HPC origin, supporting the concept that human hepatocarcinogenesis may originate from the transformation of HPCs.