Abstract
Objective. The intrahepatic stem cells, also known as hepatic progenitor cells (HPCs), are able to differentiate into hepatocytes and bile duct epithelia. By exposure of different injuries and different hepatocarcinogenic regimens, the mature hepatocytes can no longer effectively regenerate; stem cells are involved in the pathogenesis of hepatocellular carcinoma. Methods. Immunohistochemistry was performed on 107 paraffin-embedded hepatocellular carcinoma specimens with the marker of hepatocyte and hepatocellular carcinoma (HepPar1), biliary differentiation (CK7,CK19), haemopoietic stem cell (HSC) (c-kit/CD117, CD34, and Thy-1/CD90), HPC specific markers (OV-6), and Ki-67, p53 protein. Results. HPCs can be identified in the tumor nodules, around the edge of tumor nodules, and in the portal tracts of the paracirrhosis nodules being positive in HepPar1, CK7, CK19, and OV-6, but they failed to immunostain with CD117, CD34, and CD90. The HPCs positive in Ki-67 are observed in the tumor and paracirrhosis tissues. In 107 specimens, 40.2% (43/107) HCC tissues expressed p53 protein, lower than that of the HPCs around the tumor nodules (46.7%, 50/107) and much higher than that of the HPCs around the paracirrhosis nodules (8.41%, 9/107). Conclusion. Human hepatocellular carcinogenesis may be based on transformation of HPCs, not HSCs, through the formation of the transitional cells (hepatocyte-like cells and bile ductal cells).
Highlights
In vitro, the cellular response of the liver to different injuries and different hepatocarcinogenic regimens involves cells at different levels in the liver lineage: the mature hepatocyte, the intrahepatic stem cell, and the haemopoietic stem cell (HSC) in the liver derived from circulating bone marrow stem cells [1, 2]
Immunohistochemistry was performed on these sections with mouse monoclonal antibodies: the marker of hepatocyte and hepatocellular carcinoma (HCC) (HepPar1), the markers of biliary differentiation (CK7 and CK19), the markers of HSC, the hepatic progenitor cells (HPCs) specific markers (OV-6), Ki-67, and p53 protein
There exist two types of stem cells: the haemopoietic stem cell from bone marrow and the intrahepatic stem cell existing in the Canals of Hering (CoH) [3, 13, 17, 18]
Summary
The cellular response of the liver to different injuries and different hepatocarcinogenic regimens involves cells at different levels in the liver lineage: the mature hepatocyte, the intrahepatic stem cell, and the haemopoietic stem cell (HSC) in the liver derived from circulating bone marrow stem cells [1, 2] Each of these cell types may produce mature cells [3,4,5], but the mature hepatocytes play the main role in the liver regeneration. The intrahepatic stem cell, known as hepatic progenitor cells (HPCs), are small epithelial cells with an oval nucleus and a small rim of eosinophilic cytoplasm that variably display features of both hepatocytes and bile duct epithelium. The monoclonal antibody OV-6 is useful in identifying these cells [14]
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