Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde.

The authors studied histochemically the morphologic features of proliferating hepatocytes positive for proliferating cell nuclear antigen (PCNA/cyclin) to analyze the process of liver regeneration in embedded tissues fixed with formaldehyde using an anti-PCNA/cyclin monoclonal antibody. In liver specimens from patients with acute viral hepatitis (AVH) and confluent necrosis, many small basophilic hepatocytes surrounding large clear hepatocytes were positively stained in the areas next to the confluent necrosis. Therefore these small hepatocytes may be daughter cells derived from large clear hepatocytes that probably enter the mitotic cell cycle repeatedly to repair a large necrotic area. In the case of AVH with spotty necrosis, the positively stained hepatocytes were scattered around the necrotic foci. In the liver specimens from patients with chronic active hepatitis, most of the positively stained hepatocytes were located next to the necrotic area. As for cirrhosis of the liver, the number of hepatocytes positive for PCNA/cyclin varied greatly in different pseudolobules, and in the specimens of hepatocellular carcinoma (HCC), the HCC cells positive for PCNA/cyclin were detected throughout the cancer nests.

[1]  M. Kojiro,et al.  Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC. , 2008, Liver.

[2]  T. Nakamura,et al.  Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. , 1990, Biochemical and biophysical research communications.

[3]  P. Galand,et al.  Cyclin/PCNA immunostaining as an alternative to tritiated thymidine pulse labelling for marking S phase cells in paraffin sections from animal and human tissues , 1989, Cell and tissue kinetics.

[4]  B. Calabretta,et al.  Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. , 1988, Science.

[5]  R. Bravo,et al.  Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites , 1987, The Journal of cell biology.

[6]  R. Bravo,et al.  Cyclin/PCNA is the auxiliary protein of DNA polymerase-δ , 1987, Nature.

[7]  E. Tan,et al.  Monoclonal antibodies to a nuclear protein (PCNA/cyclin) associated with DNA replication. , 1987, Experimental cell research.

[8]  J. Gray,et al.  Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. , 1986, Experimental cell research.

[9]  J. Celis,et al.  Cell cycle-dependent variations in the distribution of the nuclear protein cyclin proliferating cell nuclear antigen in cultured cells: subdivision of S phase. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Bravo,et al.  Changes in the nuclear distribution of cyclin (PCNA) but not its synthesis depend on DNA replication. , 1985, The EMBO journal.

[11]  T. Kinsella,et al.  Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. , 1983, The Journal of clinical investigation.

[12]  H. Gratzner,et al.  Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. , 1982, Science.

[13]  J. Celis,et al.  A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells , 1980, The Journal of cell biology.

[14]  E. Tan,et al.  Autoantibody to a nuclear antigen in proliferating cells. , 1978, Journal of immunology.

[15]  D. Miller,et al.  Acinar distribution of liver cell regeneration after selective zonal injury in the rat. , 1978, Gastroenterology.

[16]  G. Karvountzis,et al.  Long Term Follow-Up Studies of Patients Surviving Fulminant Viral Hepatitis , 1974 .

[17]  I. Tannock,et al.  Cell proliferation in human melanoma. , 1970, The Journal of clinical investigation.