Cellular Differentiation During Neoplastic Development in the Liver

  • Peter Bannasch
  • Harald Enzmann
  • Youbing Ruan
  • Edgar Weber
  • Heide Zerban
Conference paper


Human and experimental liver tumors are classified according to the similarity in morphology and histological arrangement of their cells to specific normal counterparts. Thus, hepatocellular, cholangiocellular and diverse mesenchymal tumors are distinguished. This histogenetic classification was established by light microscopy. It has been supported by many electron microscopical results and more recently also by immunohistochemical investigations of certain cytoskeletal components, especially the so-called intermediate filaments.


Glycogen Phosphorylase Anabolic Androgenic Steroid Primary Liver Tumor Peliosis Hepatis Neoplastic Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Altmann, H.W., 1978, Pathology of human liver tumors, in: “Primary Liver Tumors,” H. Remmer, H.M. Bolt, P. Bannasch, and H. Popper, eds., MTP Press, Lancaster.Google Scholar
  2. Altmann, H.W., 1984, Neubildungen der Leber, Verh. Dtsch. Krebs.Ges., 5:423.Google Scholar
  3. Bannasch, P., 1968, The cytoplasm of hepatocytes during carcinogenesis. Light and electron microscopic investigations of the nitrosomorpholine-intoxicated rat liver, Rec. Res. Cancer Res., 19:1.Google Scholar
  4. Bannasch, P., 1986, Preneoplastic lesions as end points in carcinogenicity testing. I. Hepatic preneoplasia, Carcinogenesis, 7:689.PubMedCrossRefGoogle Scholar
  5. Bannasch, P. and Zerban, H., 1986, Pathogenesis of primary liver tumors induced by chemicals, Rec. Res. Cancer Res., 100:1.Google Scholar
  6. Bannasch, P. and Zerban, H., 1987, Modulation of hepatocellular phenotype and proliferation in liver cirrhosis, in: “Liver Cirrhosis”, MTP Press, Lancaster.Google Scholar
  7. Bannasch, P., Mayer, D., and Hacker, H.J., 1980a, Hepatocellular glycogenosis and hepatocarcinogenesis, Biochim. Biophys. Acta, 605:217.Google Scholar
  8. Bannasch, P., Zerban, H., Schmid, E., and Franke, W.W., 1980b, Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate-sized filaments, Proc. Natl. Acad. Sci. USA, 77:4948.CrossRefGoogle Scholar
  9. Bannasch, P., Bloch, H., and Zerban, H., 1981a, Spongiosis hepatis. Specific changes of the perisinusoidal liver cells induced in rats by N-nitrosomorpholine, Lab. Invest., 44:252.Google Scholar
  10. Bannasch, P., Zerban, H., Schmid, E., and Franke, W.W., 1981b, Characterization of cytoskeletal components in epithelial and mesenchymal liver tumors by electron and immunofluorescence microscopy, Virchows Arch. (Cell Pathol.), 36:139.CrossRefGoogle Scholar
  11. Bannasch, P., Hacker, H.J., Klimek, F., and Mayer, D., 1984, Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogenesis, Adv. Enzyme Regul., 22:97.PubMedCrossRefGoogle Scholar
  12. Bannasch, P., Benner, U., Enzmann, H., and Hacker, H.J., 1985a, Tigroid cell foci and neoplastic nodules in the liver of rats treated with a single dose of aflatoxin B1, Carcinogenesis, 6:1641.CrossRefGoogle Scholar
  13. Bannasch, P., Benner, U., and Zerban, H., 1985b, Cholangio fibroma and cholangiocarcinoma, liver, rat, in: “Digestive System,” T.C. Jones, U. Mohr, and R.D. Hunt, eds., Springer Verlag, Berlin-Heidelberg-New York-Tokyo.Google Scholar
  14. Bannasch, P., Moore, M.A., Hacker, H.J., Klimek, F., Mayer, D., Enzmann, H., and Zerban, H., 1985c, Potential significance of phenotypic instability in focal and nodular liver lesions induced by hepatocar cinogens, in: “Hepatology: A Festschrift for Hans Popper,” H. Brunner and H. Thaler, eds., Raven Press, New York.Google Scholar
  15. Bannasch, P., Wayss, K., and Zerban, H., 1985d, Peliosis hepatis, rodents, in: “Digestive System,” T.C Jones, U. Mohr, and R.D. Hunt, eds., Springer-Verlag, Berlin-Heidelberg-New York-Tokyo.Google Scholar
  16. Bannasch, P., Zerban, H., and Fügel, H.J., 1985e, Spongiosis hepatis, rat, in: “Digestive System,” T.C. Jones, U. Mohr, and R.D. Hunt, eds., Springer-Verlag, Berlin-Heidelberg-New York-Tokyo.Google Scholar
  17. Bannasch, P., Zerban, H., and Hacker, H.J., 1985f, Foci of altered hepatocytes, rat, in: “Digestive System,” T.C. Jones, U. Mohr, and R.D. Hunt, eds., Springer-Verlag Berlin-Heidelberg-New York-Tokyo.Google Scholar
  18. Beasly, R.P., Hwang, L.-Y., Lin, C.-C., and Chien C.-S., 1981, Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22,707 men in Taiwan, Lancet, 2:1129.CrossRefGoogle Scholar
  19. Cain, H., 1978, Liver cell carcinoma in infancy and childhood, in: “Primary Liver Tumors,” H. Remmer, H. Bolt, P. Bannasch, and H. Popper, eds., MTP Press, Lancaster.Google Scholar
  20. Coire, C.I., Qizilbash, A.H., and Castelli, M.F., 1987, Hepatic adenomata in type laglycogen storage disease, Arch. Pathol. Lab. Med., 111:166.PubMedGoogle Scholar
  21. Ehemann, V., Mayer, D., Hacker, H.J., and Bannasch, P., 1986, Loss of adenylate cyclase activity in preneoplastic and neoplastic lesions induced in rat liver by N-nitrosomorpholine, Carcinogenesis, 7:567.PubMedCrossRefGoogle Scholar
  22. Enzmann, H. and Bannasch, P., 1986, Sequential phenotypic conversion of hepatocytes during carcinogenesis, Cancer Lett., 30:S67.Google Scholar
  23. Farber, E., 1984, Precancerous steps in carcinogenesis. Their physiological adaptive nature, Biochim. Biophys. Acta, 738:171.PubMedGoogle Scholar
  24. Farber, E., and Sarma, D.S.R., 1987, Hepatocarcinogenesis: A dynamic cellular perspective, Lab. Invest., 56:4.PubMedGoogle Scholar
  25. Fischer, G., Hartmann, H., Droese, M., Schauer, A., and Bock, K.W., 1986, Histochemical and immunohistochemical detection of putative preneoplastic liver foci in woman after long-term use of oral contraceptives Virchows Arch. (Cell Pathol.), 50:321.CrossRefGoogle Scholar
  26. Goldsworthy, T.L., Hanigan, M.H., and Pitot, H.C., 1986, Models of hepatocarcinogenesis in the rat — contrasts and comparisons, CRC Critical Rev. Toxicol., 17:61.CrossRefGoogle Scholar
  27. Hacker, H.J., Moore, M.A., Mayer, D., and Bannasch, P., 1982, Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver, Carcinogenesis, 3:1265.PubMedCrossRefGoogle Scholar
  28. Hann, H.L., Kim, C.Y., London, W.T., Whitford, P., and Blumberg, B.S., 1982, Hepatitis B virus and primary hepatocellular carcinoma: family studies in Korea, Int. J. Cancer, 30:47.PubMedCrossRefGoogle Scholar
  29. Heine, W.D., 1981, Experimentelle und menschliche hepatozelluläre Lebertumoren und ihre Vostufen — histologische, histochemische und zellkinetische Charakteristika, in: “Experimentelle und klinische Hepatologie,” O. Zelder, H.D. Röher, M. Fischer, and J. Ch. Bode, eds., F.K. Schattauer Verlag, Stuttgart-New York.Google Scholar
  30. Heinzelmann, D., 1986, Modulation der Nitrosamin induzierten Hepatocarcinogenese der Ratte durch Dehydroepian-drosteron. Inauguraldissertation, Universität Heidelberg.Google Scholar
  31. Hirota, N., Hamazaki, M., and Williams, G.M., 1982, Resistance to iron accumulation and presence of hepatitis B surface antigen in preneoplastic and neoplastic lesions in human hemochromatotic livers, Hepatogastroenterol., 29:49.Google Scholar
  32. Jones, G., and Butler, W.H., 1978, Light microscopy of rat hepatic neoplasia, in: “Rat Hepatic Neoplasia,” P.M. Newberne and W.H. Butler, eds., MIT Press, Cambridge.Google Scholar
  33. Karhunen, P.J., and Penttilä, A., 1987, Preneoplastic lesions of human liver, Hepato-gastroenterol., 34:10.Google Scholar
  34. Klimek, F., Mayer, D., and Bannasch, P., 1984, Biochemical microanalysis of glycogen content and glucose-6-phosphate dehydrogenase activity in focal lesions or rat liver induced by N-nitrosomorpholine, Carcinogenesis, 5:265.PubMedCrossRefGoogle Scholar
  35. Limmer, J., Mohr, W., Bittner, R., Krautzberger, W., und Beger, H.G., 1985, Hepatozelluläres Karzinom auf dem Boden einer Glycogenose Typ von Giercke, Z. Gastroenterol., 23:303.Google Scholar
  36. Melbye, M., Skinhøj, P., Nielsen, H.H., Vestergaard, B.F., Ebbesen, P., Hansen, J.P.H., and Biggar, R.J., 1984, Virus-associated cancers in Greenland: Frequent hepatitis B virus infection but low primary hepatocellular carcinoma incidence, J. Natl. Cancer Inst., 73:1267.PubMedGoogle Scholar
  37. Messing, A., Chen, H.Y., Palmiter, R.D., and Brinster, R.L., 1985, Peripheral neuropathies, hepatocellular carcinomas and islet cell adenomas in transgenic mice, Nature, 316:461.PubMedCrossRefGoogle Scholar
  38. Montesano, R., Bartsch, H., Vaino, H., Wilbourn, J., and Yamasaki, H., eds., 1986, “Long-term and short-term assays for carcinogens: A critical appraisal”, IARC Scientifique Publications, N°. 83, Lyon.Google Scholar
  39. Moore, M.A., and Kitagawa, T., 1986, Hepatocarcinogenesis in the rat; the effect of the promoters and carcinogens in vivo and in vitro, Int. Rev. Cytol., 101:125.PubMedCrossRefGoogle Scholar
  40. Moore, M.A., Mayer, D., and Bannasch, P., 1982, The dose-dependence and sequential appearance of putative preneoplastic populations induced in the rat liver by stop experiments with N-nitrosomorpholine, Carcinogenesis, 3:1429.PubMedCrossRefGoogle Scholar
  41. Moore, M.A., Fukushima, S., Ichihara, A., Sato, K., and Ito, N., 1986, Intestinal metaplasia and altered enzyme expression in propyl-nitrosamine-induced Syrian hamster cholangiocellular and gallbladder lesions, Virchows Arch. (Cell Pathol.), 51:29.CrossRefGoogle Scholar
  42. Mori, H., Tanaka, T., Sugie, S., Takahashi, M., and Williams, G., 1982, DNA content of liver cell nuclei of N-2-fluorenylacetamide-induced altered foci and neoplasms in rats and human hyperplastic foci, J. Natl. Cancer Inst., 69:1277.PubMedGoogle Scholar
  43. Nadell, J., and Kosek, J., 1977, Peliosis hepatis. Twelve cases associated with oral androgen therapy, Arch. Pathol. Lab. Med., 101:405.PubMedGoogle Scholar
  44. Osborn, M. and Weber, K., 1986, Intermediate filament proteins: a multigene family distinguishing major cell lineages, trends Biochem. Sci., 11:469.CrossRefGoogle Scholar
  45. Peers, F., Bosch, X., Kaldor, J., Linselle, A., and Pluijomen, M., 1987, Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland, Int. J. Cancer, in press.Google Scholar
  46. Peraino, C., Richards, W.L., and Stevens, F.J., 1983, Multistage hepatocarcinogenesis, in: “Mechanisms of Tumor Promotion,” T.J. Slaga, ed., CRC Press, Boca Raton.Google Scholar
  47. Popper, H., Maltoni, C., Selikoff, I.J., Squire, R.A., and Thomas, L.B., 1977, Comparison of neoplastic hepatic lesions in man and experimental animals, in: “Origin of Human Cancer,” Book C, Human Risk Assessment, H.H. Hiat, J.D. Watson, and J.A. Winsten, eds., Cold Spring Harbor Laboratories, Cold Spring Harbor.Google Scholar
  48. Popper, H., Thomas, L.B., Telles, N.C., Falk, H., and Selikoff, I.J., 1978, Development of hepatic angiosarcoma in man induced by vinyl chloride, thorotrast, and arsenic, Am. J. Pathol., 92:349.PubMedGoogle Scholar
  49. Rabes, H.M., 1983, Development and growth of early preneoplastic lesions induced in the liver by chemical carcinogens, J. Cancer Res. Clin. Oncol., 106:85.PubMedCrossRefGoogle Scholar
  50. Ramaekers, F.C.S., Puts, J.J.G. Kant, A., Moesker, O., Jap, P.H.K, and Vooijs, G.P., 1982, The use of antibodies directed against intermediate filaments in the characterization of human tumors, Cold Spring Harbor Symposia on Quantitative Biology, 46:331.PubMedGoogle Scholar
  51. Ruan, Y.-B., 1985, Zytochemische und elektronenmikroskopische Charakterisierung des zellulären Phänotyps adenoider Lebertumoren, Inaugural-Dissertation, Universität Heidelberg.Google Scholar
  52. Scherer, E., 1984, Neoplastic progression in experimental hepatocarcinogenesis, Biochim. Biophys. Acta, 738:219.PubMedGoogle Scholar
  53. Schröter, C., Parzefall, W., Schröter, H., and Schulte-Hermann, R., 1987, Dose-response studies on the effects of γ-, β-, and α- hexachlorohexane on putative preneoplastic foci, monooxygenases, and growth in rat liver, Cancer Res., 47:80.PubMedGoogle Scholar
  54. Seelmann-Eggebert, G., Mayer, D., Mecke, D., and Bannasch, P., 1987, Expression and regulation of glycogen phosphorylase in preneoplastic and neoplastic hepatic lesions in rats, Virchows Arch. B (Cell Path.), 53:44.CrossRefGoogle Scholar
  55. Stewart, H.L., Williams, G., Keysser, C.H., Lombard, L.S., and Montali, R.J., 1980, Histologic typing of liver tumors of the rat, J. Natl. Cancer Inst., 65:179.Google Scholar
  56. Tatematsu, M., Kaku, T., Medline, A., and Farber, E., 1985, Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylaminofluorene, Lab. Invest., 52:354.PubMedGoogle Scholar
  57. Terao, K., and Nakano, M., 1974, Cholangiofibrosis induced by short-term feeding of 3′-methyl-4-(dimethylamino) azobenzene: an electron microscopic observation, Gann, 65:249.PubMedGoogle Scholar
  58. Thamavit, W., Kongkanuntn, R., Tiwawech, D., and Moore, M.A., 1987, Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian golden hamsters, Virchows Arch B, submitted.Google Scholar
  59. Tiollais, P., Pourcel, C., and Dejean, A., 1985, The hepatitis B virus, Nature, 317:489.PubMedCrossRefGoogle Scholar
  60. Tu, J., Gao, R., Zhang, D., Gu, B., Xu, G., Fang, R., Pan, J., Yu, H., Huang, Y., and Zhou, X., 1987, Risk factors of primary liver cancer in the high prevalence area Chongming County — results from a five years follow up, in: “Cancer of the Liver, Esophagus, and Nasopharynx,” G. Wagner and You-Hui Zhang, eds., Springer, Berlin-Heidelberg-New York-Tokyo.Google Scholar
  61. Wake, K., 1980, Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs, Int. Rev. Cytol., 66:303.PubMedCrossRefGoogle Scholar
  62. Ward, J.M., 1984, Morphology of potential preneoplastic hepatocyte lesions and liver tumors in mice and a comparison with other species, in: “Mouse Liver Neoplasia,” J.A. Popp, ed., Hemisphere Publishing Corporation, Washington-New York-London.Google Scholar
  63. Wayss, K., Bannasch, P., Mattern, J., and Volm, M., 1979, Vascular liver tumors induced in Mastomys (Praomys) natalensis by single dimethylnitrotrosamine, J. Natl. Cancer Inst., 62:1199.PubMedGoogle Scholar
  64. Weber, E., Heinzelmann, D., and Bannasch, P., 1986, The The effect of DHEA on peroxisomes in nitrosamine-treated rat liver, Europ. J. Cell Biol., 41 (Suppl 14):44.Google Scholar
  65. Weber, G., 1977, Enzymology of cancer cells, Parts 1 and 2, New Engl. J. Med., 296:486.PubMedCrossRefGoogle Scholar
  66. Willis, R.A., 1953, “Pathology of Tumors”, 2nd Edition, Butterworth & Co, London.Google Scholar
  67. Zerban, H., Rabes, H.M., and Bannasch, P., 1985, Kinetics of cell proliferation during hepatocarcinogenesis, Europ. J. Cancer Clin. Oncol., 21.:1424.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Peter Bannasch
    • 1
  • Harald Enzmann
    • 1
  • Youbing Ruan
    • 1
  • Edgar Weber
    • 1
  • Heide Zerban
    • 1
  1. 1.Institut für Experimentelle PathologieDeutsches KrebsforschungszentrumHeidelbergGermany

Personalised recommendations