Serological Tumor Markers in Hepatocellular Carcinoma

  • Norio Sawabu
  • Nobu Hattori


A number of substances have been reported to be tumor markers, but many are limited to research use. In the case of hepatocellular carcinoma (HCC), however, several markers are clinically useful, of which α-fetoprotein (AFP) is perhaps one of the best.


Sugar Chain Hepatobiliary Disease Metastatic Liver Cancer Benign Liver Disease Alkaline Phosphatase Isoenzyme 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ruoslahti E, Seppälä M (1979) α-Fetoprotein in cancer and fetal development. Adv Cancer Res 29:275–346PubMedCrossRefGoogle Scholar
  2. 2.
    Hirai H, Nishi S, Watanabe H, Tsukada Y (1973) Some clinical, experimental, and clinical investigations of α-fetoprotein. In: Hirai H, Miyaji T (eds) α-Fetoprotein and hepatoma. Gann Monogr Cancer Res 14. Japan Scientific Societies Press, Tokyo, pp 19–34Google Scholar
  3. 3.
    Okuda K (1976) Clinical aspect of hepatocellular carcinoma-analysis of 134 cases. In: Okuda K, Peters RL (eds) Hepatocellular carcinoma. Wiley, New York, pp 387–405Google Scholar
  4. 4.
    Chen DS, Sung JL, Sheu JC, Lai MY, How SW, Hsu HC, Lee CS, Wei TC (1984) Serum α-fetoprotein in the early stage of human hepatocellular carcinoma. Gastroenterology 86:1404–1409PubMedGoogle Scholar
  5. 5.
    Sheu JC, Sung JL, Chen DS, Yang PM, Lai MY, Lee CS, Hsu HC, Chuang CN, Yang PC, Wang TH, Lin JC, Lee CZ (1985) Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications. Gastroenterology 89:259–266PubMedGoogle Scholar
  6. 6.
    Kobayashi K, Sugimoto T, Makino H, Kumagai M, Unoura M, Tanaka N, Kato Y, Hattori N (1985) Screening methods for early detection of hepatocellular carcinoma. Hepatology 5:1100–1105PubMedCrossRefGoogle Scholar
  7. 7.
    Kubo Y, Okuda K, Musha H, Nakashima T (1978) Detection of hepatocellular crcinoma during a clinical follow-up of chronic liver disease. Gastroenterology 74: 578–582PubMedGoogle Scholar
  8. 8.
    Sawabu N, Wakabayashi T, Ozaki K, Toya D, Yoneshima M, Kidani H, Hattori N, Ishii M (1985) Serum tumor markers in patients with hepatocellular carcinoma: Diagnosis of α-fetoprotein-low or-negative patients. Gastroent Jap 20:209–215Google Scholar
  9. 9.
    Yoshima H, Mizuochi T, Ishii M, Kobata A (1980) Structure of the asparagine-linked sugar chains of α-fetoprotein purified from human ascites fluid. Cancer Res 40:4276–4281PubMedGoogle Scholar
  10. 10.
    Yamashita K, Hitoi A, Tsuchida Y, Nishi S, Kobata A (1983) Sugar chain of α-fetoprotein produced in human yolk sac tumor. Cancer Res 43:4691–4695PubMedGoogle Scholar
  11. 11.
    Aoyagi Y, Suzuki Y, Isemura M, Soga K, Ozaki T, Ichida T, Inoue K, Sasaki H, Ichida F (1984) Differential reactivity of α-fetoprotein with lectins and evaluation of its usefulness in the diagnosis of hepatocellular carcinoma. Jpn J Cancer Res (Gann) 75: 809–815Google Scholar
  12. 12.
    Taketa K, Izumi M, Ichikawa E (1983) Distinct molecular species of human α-fetoprotein due to differential affinities to lectins. Ann NY Acad Sci 417:61–68PubMedCrossRefGoogle Scholar
  13. 13.
    Ishiguro T, Sugitachi I, Sakaguchi H, Itani S (1985) Serum α-fetoprotein subfractions in patients with primary hepatoma or hepatic metastasis of gastric cancer. Cancer 55:156–159PubMedCrossRefGoogle Scholar
  14. 14.
    Bellet DH, Wands JR, Isselbacher KJ, Bohunon C (1984) Serum α-fetoprotein levels in human disease: perspective from a highly specific monoclonal radioimmunoassay. Proc Natl Acad Sci USA 81:3869–3873PubMedCrossRefGoogle Scholar
  15. 15.
    Fiala S, Fiala AE, Dixon B (1972) γ-Glutamyl transpeptidase in transplantable chemically induced rat hepatomas and “spontaneous” mouse hepatomas. J Natl Cancer Inst 48:1393–1401PubMedGoogle Scholar
  16. 16.
    Kalengayi MMR, Ronchi G, Desmet VJ (1975) Histochemistry of γ-glutamyl transpeptidase in rat liver during aflatoxin B1-induced carcinogenesis. J Natl Cancer Inst 55: 579–582PubMedGoogle Scholar
  17. 17.
    Taniguchi N, Saito K, Takakuwa E (1975) γ-Glutamyltransferase from azodye induced hepatoma and fetal rat liver, similarities in their kinetic and immunological properties. Biochim Biophys Acta 391:265–271PubMedCrossRefGoogle Scholar
  18. 18.
    Sells MA, Katyal SL, Sell S, Shinozuka H, Lombardi B (1979) Induction of foci of altered, γ-glutamyltranspeptidase-positive hepatocytes in carcinogen-treated rats fed a choline-deficient diet. Br J Cancer 40:274–283PubMedCrossRefGoogle Scholar
  19. 19.
    Tsuchida S, Hoshino K, Sato T, Ito N, Sato K (1979) Purification of γ-glutamyltranferases from rat hepatomas and hyperplastic hepatic nodules, and comparison with the enzyme from rat kidney. Cancer Res 39:4200–4205PubMedGoogle Scholar
  20. 20.
    Albert Z, Rzucidlo Z, Starzyk H (1970) Comparative biochemical and histochemical studies on the activity of gamma-glutamyl transpeptidase in the organs of fetuses, newborns and adult rats. Acta Histochem 37:34–49PubMedGoogle Scholar
  21. 21.
    Sawabu N, Nakagen M, Yoneda M, Makino H, Kameda S, Kobayashi K, Hattori N, Ishii M (1978) Novel γ-glutamyl transpeptidase isoenzyme specifically found in sera of patients with hepatocellular carcinoma Jpn J Cancer Res (Gann) 69:601–605Google Scholar
  22. 22.
    Sawabu N, Nakagen M, Ozaki K, Wakabayashi T, Toya D, Hattori N, Ishii M (1983) Clinical evaluation of specific γ-GTP isoenzyme in patients with hepatocellular carcinoma. Cancer 51:327–331PubMedCrossRefGoogle Scholar
  23. 23.
    Kojima J, Kanatani M, Nakamura N, Kashiwagi T, Tohjoh F, Akiyama M (1980) Electrophoretic fractionation of serum γ-glutamyl transpeptidase in human hepatic cancer. Clin Chim Acta 106: 165–172PubMedCrossRefGoogle Scholar
  24. 24.
    Kew MC, Wolf P, Whittaker D, Rowe P (1984) Tumor-associated isoenzymes of γ-glutamyl transpeptidase in the serum of patients with hepatocellular carcinoma. Br J Cancer 50:451–455PubMedCrossRefGoogle Scholar
  25. 25.
    Toya D, Sawabu N, Ozaki K, Wakabayashi T, Nakagen M, Hattori N (1983) Purification of γ-GTP from human hepatocellular carcinoma, and comparison with enzyme from kidney. Ann NY Acad Sci 417:89–96CrossRefGoogle Scholar
  26. 26.
    Sawabu N, Toya D, Ozaki K, Wakabayashi T, Nakagen M, (1983) Clinical value and some properties of novel γ-GTP isoenzyme specific to sera of hepatocellular carcinoma. In: Makita A, Tsuiki S, Fujii S, Warren L (eds) Membrane alterations in cancer. Gann Monogr Cancer Res 29. Japan Scientific Societies Press, Tokyo, pp 291–298CrossRefGoogle Scholar
  27. 27.
    Shaw LM, Petersen-Archer L, London JW, Marsh E (1980) Electrophoretic, kinetic, and immunoinhibition properties of γ-glutamyl-transferase from various tissues compared. Clin Chem 26:1523–1527PubMedGoogle Scholar
  28. 28.
    Huseby NE (1981) Separation and characterization of human γ-glutamyltransferases. Clin Chim Acta 111:39–45PubMedCrossRefGoogle Scholar
  29. 29.
    Miura T, Matsuda Y, Tsuji, A, Katunuma N (1981) Immunological cross-reactivity of γ-glutamyltranspeptidases from human and rat kidney, liver and bile. J Biochem 89:217–222PubMedGoogle Scholar
  30. 30.
    Yamashita K, Hitoi A, Taniguchi N, Yokosawa N, Tsukada Y, Kobata A (1983) Comparative study of the sugar chains of γ-glutamyltranspeptidases purified from rat liver and rat AH-66 hepatoma cells. Cancer Res 43:5059–5063PubMedGoogle Scholar
  31. 31.
    Hitoi A, Yamashita K, Ohkawa J, Kobata A (1984) Application of a phaseolus vulgaris erythroagglutinating lectin agarose column for the specific detection of human hepatoma γ-glutamyl transpeptidase in serum. Jpn J Cancer Res (Gann) 75:301–304Google Scholar
  32. 32.
    Fishman WH, Inglis NR, Stolbach LL, Krant MJ (1986) A serum alkaline phosphatase isoenzyme of human neoplastic cell origin. Cancer Res 28:150–154Google Scholar
  33. 33.
    Nakayama T, Yoshida M, Kitamura M (1970) L-leucine sensitive, heat-stable alkaline-phospha-tase isoenzyme detected in a patient with pleuritis carcinomatosa. Clin Chim Acta 30:546–548PubMedCrossRefGoogle Scholar
  34. 34.
    Warnock ML, Reisman R (1969) Variant alkaline phosphatase in human hepatocellular cancers. Clin Chim Acta 24: 5–11PubMedCrossRefGoogle Scholar
  35. 35.
    Nakagen M, Sawabu N, Sendai H, Wakabayashi T, Ozaki K, Toya D, Hattori N (1980) Evaluation of alkaline phosphatase isoenzyme separated by polyacrylamide gradient gel electrophoresis: Special reference to variant alkaline phosphatase. Jpn J Gastroent 77:1937–1940 (in Japanese)Google Scholar
  36. 36.
    Suzuki H, Lino S, Endo Y, Torii M, Miki K, Oda T (1975) Tumor-specific alkaline phosphatase in hepatoma. Ann NY Acad Sci 259: 307–316PubMedCrossRefGoogle Scholar
  37. 37.
    Higashino K, Kudo S, Ohtani R, Yamamura Y, Honda T, Sakurai J (1975) A hepatomaassociated alkaline phosphatase, the Kasahara isoenzyme, compared with one of the isoenzyme of FL ammion cells. Ann NY Acad Sci 259:337–346PubMedCrossRefGoogle Scholar
  38. 38.
    Higashino K, Kudo S, Ohtani R, Yamamura Y (1976) Further observation on Kasahara isoenzyme in patients with malignant diseases. Jpn J Cancer Res (Gann) 67:909–911Google Scholar
  39. 39.
    Blanchard RA, Furie BC, Jorgensen M, Kruger SF, Furie B (1981) Acquired vitamin K-dependent carboxylation deficiency in liver disease. N Engl J Med 305:242–248PubMedCrossRefGoogle Scholar
  40. 40.
    Liebmen HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, Coleman MS, Furie B (1984) Des-γ-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 310:1427–1431CrossRefGoogle Scholar

Copyright information

© Springer Japan 1987

Authors and Affiliations

  • Norio Sawabu
    • 1
  • Nobu Hattori
    • 2
  1. 1.Department of Internal Medicine, Cancer Research InstituteKanazawa UniversityKanazawa, 920Japan
  2. 2.First Department of Internal MedicineKanazawa University School of MedicineKanazawa, 920Japan

Personalised recommendations