Summary
A combined hepatocellular-cholangiocarcinoma (CHC) of transitional subtype and the surrounding cirrhotic liver tissue were investigated immunocytochemically by monoclonal antibodies specific for each of the keratin polypeptides 7, 8, 18 and 19. Different keratin subsets were found in different parts of the tumour. The hepatocellular component reveals keratins 8 and 18, with the bordering cells of trabecular formations additionally expressing keratins 7 and 19. The same keratins i.e. 7, 8, 18, 19 were found in normal bile duct epithelium as well as in cholangiocarcinomatous and transitional areas of hepatocellular and cholangiocellular differentiation. Normal hepatocytes express only keratin 8 and 18. In cirrhotic liver some modified hepatocytes additionally express keratin 7. When ductal transformation is observed in the marginal parts of portal tracts and fibrous septa the keratin polypeptide pattern mimics that of bile duct epithelium. The cholangiocellular metaplasia of hepatocytes observed here correlates well with findings in hepato-organogenesis and hepatocarcinogenesis and suggests that the transitional subtype of combined hepatocellular-cholangiocarcinoma is a variant of hepatocellular carcinoma.
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References
Altmann HW (1978): Pathology of human liver tumors. In: RemmerH, Bolt HM, Bannasch P, Popper H (eds) Primary liver tumors. Lancaster, MTP Press Ltd, pp 53–71
Anthony PP (1973) Primary carcinoma of the liver: A study of 282 cases in Ugandan Africans. J Pathol110:37–48
Berman MM, Libbey NP, Foster JH (1980) Hepatocellular carcinoma: polygonal cell type with fibrous stroma. An atypical variant with a favourable prognosis. Cancer: 1448-1455
Bosslet K, Lüben G, Schwarz A, Hundt E, Harthus HP, Seiler FR, Muhrer C, Klöppel G, Kayser K, Sedlacek HH(1985) Immunohistochemical localization and molecular characteristics of three monoclonal antibody-defined epitopes detectable on carcinoembryonal antigen (CEA). Int J Cancer 36:75–84
Craig JR, Peters RL, Edmondson HA, Omata M(1980) Fibrolamellar carcinoma of the liver: A tumor of adolescents and young adults with distinctive clinicopathologic features. Cancer 46:372–379
Debus E, Weber K, Osborn M(1982) Monoclonal cytokeratin antibodies that distinguish simple from stratified squamous epithelia: Characterization on human tissues. EMBO 2:1641–1647
Debus E, Weber K, Osborn M (1983 a) Monoclonal antibodies to desmin, the muscle-specific intermediate filament protein. EMBO J 2:2305–2312
Debus E, Weber K, Osborn M (1983 b) Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides. Differentiation 25:193–203
Debus E, Moll R, Franke WW, Weber K, Osborn M (1984) Immunohistological distinction of human carcinomas by cytokeratin typing with monoclonal antibodies. Am J Pathol 114:121–130
Denk H, Krepier R, Lackinger E, Artlieb U, Franke WW (1982) Biochemical and immunocytochemical analysis of the intermediate filament cytoskeleton in human hepatocellular carcinomas and in hepatic neoplastic nodules of mice. Lab Invest 46:584–596
Du Bois AM (1963) The embryonic liver. In: Rouiller CH (ed) The liver, vol 1. Academic Press, New York, pp 1–40
Edmondson HA, Peters RL (1982) Neoplasms of the liver. In: Schiff L, Schiff ER (eds) Diseases of the liver, ed. 5. Lippincott, Philadelphia, p 1101
Van Eyken P, Sciot R, van Damme B, de Wolf-Peeters C, Desmet VJ (1987) Keratin immunohistochemistry in normal human liver. Cytokeratin pattern of hepatocytes, bile ducts and acinar gradient. Virchows Arch [Pathol Anat] (1987) 412:63–72
Fischer HP, Altmannsberger M, Weber K, Osborn M (1987) Keratinpolypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects. Am J Pathol 127:530–537
Gibson JB, Sobin LH (1978) Histological typing of tumours of the liver, biliary tract and pancreas. International histological classification of tumours No. 20. WHO, Geneva
Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L (1985) Combined hepatocallular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer 55:124–135
Gould VE, Moll R, Moll I, Lee I, Franke WW (1985) Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest 52:334–353
Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Jørgensen MJ (1977) The ductal plate malformation. Acta Pathol Microbiol Scand A [Suppl] 257
Kuhlmann WD (1978) Localization of alpha-1-fetoprotein and DNA-synthesis in liver cell populations during experimental hepatocarcinogenesis in rats. Int J Cancer 21:363–380
Liver Cancer Study Group of Japan (1987) Primary liver cancer in Japan. Sixth report. Cancer 60:1400–1411
Moll R, Franke WW (1986) Cytochemical cell typing of metastatic tumors according to their cytoskeletal proteins. In: Lapis K, Liotta LA, Rabson AS (eds) Biochemistry and molecular genetics of cancer metastasis. Martinus Nijhof Publishing, Boston, pp 101–114
Moll R, Osborn M, Hartschuh W, Moll I, Mahrle G, Weber K(1986) Variability of expression and arrangement of cytokeratin and neurofilaments in cutaneous neuroendocrine carcinomas: Immunocytochemical and biochemical analysis of 12 cases. Ultrastruct Pathol 10:473–495
Nagle RB, Moll R, Weidauer H, Nemetschek H, Franke WW (1985) Different patterns of cytokeratin expression in the normal epithelia of the upper respiratory tract. Differentiation 30:130–140
Okada Y, Jinno K, Moriwaki S, Morichika S, Torigoe S, Nagashima H, Koprowsik H (1987) Expression of ABH and Lewis blood group antigens in combined hepatocellular-cholangiocarcinoma. Cancer60:345–352
Osborn M, Debus E, Weber K(1984) Monoclonal antibodies specific for vimentin. Eur J Cell Biol 34:137
Shaw G, Debus E, Weber K (1984) The immunological relatedness of neurofilament proteins of higher vertebrates. Eur J Cell Biol 34:130–136
Shaw G, Osborn M, Weber K (1986) Reactivity of a panel of neurofilament antibodies on phosphorylated and dephosphorylated neurofilaments. Eur J Cell Biol 42:1–9
Stein H, Gatter K, Asbahr H, Mason DY (1985) Use of freezedried paraffin-embedded sections for immunohistologic staining with monoclonal antibodies. Lab Invest 52:676–683
Tatematsu M, Kaku T, Medline A, Farber E (1985) Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylamino-fluorene. Lab Invest 52:354–362
Toelle HG, Weber K, Osborn M (1985) Microinjection of monoclonal antibodies specific for one intermediate filament protein in cells containing multiple keratins allow insight into composition of particular 10 nm filaments. Eur J Cell Biol 38:234–240
Tsao MS, Grisham JW (1987) Hepatocarcinomas, cholangiocarcinomas, and hepatoblastomas produced by chemically transformed cultured rat liver epithelial cells. Am J Pathol 127:168–181
Viac J, Reano A, Brochier J, Staquet MJ, Thivolet J (1983) Reactivity pattern of a monoclonal anti-keratin antibody (KL 1). J Invest Dermatol 81:351–354
Vogel AM, Gown AM, Caughlan J, Haas JE, Beckwith JB (1984) Rhabdoid tumors of the kidney contain mesenchymal specific and epithelial specific intermediate filament proteins. Lab Invest 50:232–238
Yaswen P, Thompson NL, Fausto N (1985) Oncodevelopmental expression of rat placental alkaline phosphatase. Detection in oval cells during liver carcinogenesis. Am J Pathol 121:505–513
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Fischer, HP., Doppl, W., Osborn, M. et al. Evidence for a hepatocellular lineage in a combined hepatocellular-cholangiocarcinoma of transitional type. Virchows Archiv B Cell Pathol 56, 71–76 (1988). https://doi.org/10.1007/BF02890004
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DOI: https://doi.org/10.1007/BF02890004