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α1-Foetoprotein in malignen Tumoren

α1-Foetoprotein in malignant tumors

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Summary

α1-Foetoprotein was extracted from eight primary liver cell carcinomas and three other carcinomas with α1-foetoprotein synthesis. Quantitative measurements in human tissues and in biological fluids yielded the following results:

  1. 1.

    The α1-foetoprotein concentration in human tissue varied between 12 µg/g and 630 µg/g wet weight. When the histological aspect was similar, the α1-foetoprotein level in primary tumor tissue and in metastases was in the same range.

  2. 2.

    The total α1-foetoprotein content ranged from 0.8 mg to 1415 mg/tumor.

  3. 3.

    The α1-foetoprotein concentration in the serum showed a double logarithmic correlation of 0.61 with the tumor weight, of 0.69 with the α1-foetoprotein concentration in the tumor tissue and of 0.90 with the total α1-foetoprotein amount in malignant tissue.

  4. 4.

    In an individual patient there exists a good correlation between α1-foetoprotein concentration in the serum and total α1-foetoprotein content in the tumor tissue; on the other hand, in clinical diagnosis it is impossible to calculate the unknown tumor weight or the α1-foetoprotein concentration in malignant tissue from a given serum concentration of the tumor antigen.

  5. 5.

    It could be demonstrated by extrapolation to the immunologically detectable critical tumor weight that tumors should be found theoretically in double diffusion techniques in the serum under clinical conditions when the tumors reached weights between 8 g and 335 g.

  6. 6.

    The circulating amount of α1-foetoprotein is between 2.9 and 9.9 times higher than the tumor antigen content in the malignant tumor tissue.

  7. 7.

    Eight crystalline preparations of α1-foetoprotein isolated from tumor homogenate, plasma, ascites and pleural effusions of patients with hepatocellular carcinomas showed identical antigenic determinants proved by double diffusion with 17 antisera obtained by immunization of rabbits with different pure human α1-foetoprotein preparations isolated from foetal material, tumor extracts, plasma, ascites or pleural effusions and with antisera to dog, beef and pig α1-foetoprotein. These results suggests an active elimination of α1-foetoprotein from the tumor cells in the serum. It is likely that the tumor antigen synthetized in malignant tissue and the α1-foetoprotein secreted in biological fluids have identical structures.

Zusammenfassung

α1-Foetoprotein wurde aus acht primären Leberzellcarcinomen und drei weiteren α1-Foetoproteinbildenden Tumoren extrahiert. Quantitative Bestimmungen im Tumorgewebe und im Serum ergaben folgende Ergebnisse:

  1. 1.

    Die α1-Foetoproteinkonzentration im Tumorgewebe betragt zwischen 12 µg/g und 630 µg/g Feuchtgewicht. Bei gleichem histologischen Aufbau ist der α1-Foetoproteinspiegel in Primärtumor und Metastasen gleich.

  2. 2.

    Der Gesamt-α1-Foetoproteingehalt lag zwischen 0,8 mg und 1415 mg pro Tumor.

  3. 3.

    Die α1-Foetoprotein-Serumkonzentration zeigt eine doppeltlogarithmische Korrelation mit dem Tumorgewicht von 0,61, mit der α1-Foetoproteinkonzentration im Tumorgewebe von 0,69 und mit dem Gesamtgehalt von α1-Foetoprotein im malignen Gewebe von 0,90.

  4. 4.

    Eine klinisch für den Einzelfall verwertbare Beziehung besteht nur zwischen α1-Foetoprotein-Serumkonzentration und Gesamtgehalt von α1-Foetoprotein im Tumorgewebe; es ist nicht möglich von einer bekannten Serumkonzentration auf das Tumorgewicht oder die α1-Foetoproteinkonzentration im Tumorgewebe zu schließen.

  5. 5.

    Die Extrapolation auf die theoretisch immunologisch nachweisbaren Tumorgewichte ergab, daß Tumoren mit Gewichten zwischen 8 g und 335 g unter klinischen Bedingungen in der Doppeldiffusion im Serum entdeckt werden können.

  6. 6.

    Die zirkulierende Tumorantigenmenge ist 2,9–9,9mal größer als der α1-Foetoproteingehalt in malignen Geweben.

  7. 7.

    Acht kristalline α1-Foetoproteinpräparate, die aus dem Tumorgewebe, dem Plasma, Ascites und Pleurapunktat isoliert wurden, zeigten immunologisch bei der Prüfung mit 17 Anti-α1-Foetoprotein-Seren, die durch Immunisierung mit verschiedenen menschlichen foetalen, Tumor-, Hepatomserum-, Hepatomascites-und Hepatompleurapunktat-α1-Foetoproteinen gewonnen wurden, sowie mit Anti-Hunde-, -Rinder- und-Schweine-α1-Foetoprotein-Seren eine völlige Identität der antigenen Determinanten. Diese Ergebnisse sprechen gegen eine unterschiedliche Struktur der in malignen Geweben gebildeten mit den in biologische Flüssigkeiten ausgeschwemmten Tumorantigenen und für eine aktive α1-Foetoprotein-Elimination aus dem Tumorgewebe in das Serum.

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Literatur

  1. Abelev, G. I.: Antigenic structure of chemically induced hepatomas. Progr. exp. Tumor Res. (Basel)7, 104 (1965)

    PubMed  Google Scholar 

  2. Abelev, G. I., Assekritova, I. V., Kraevsky, N. A., Perova, S. D., Perevodchikova, N. I.: Embryonal serum alpha-globulin in cancer patients: diagnostic value. Int. J. Cancer2, 551 (1967)

    PubMed  Google Scholar 

  3. Abelev, G. I., Tsvetkov, V. S., Biryllina, T. I., Elgort, D. A., Olovnikov, A. M., Goussev, A. I., Yazova, A. R., Perova, S. D., Rubtsov, I. V., Shaborina, S. V., Kantorovich, B. A., Tur, V. M., Khazanov, A. I., Levina, D. M.: Assessment of the use of highly sensitive methods of determining alpha-fetoprotein for the diagnosis of hepatocellular cancer and teratoblastoma. Biull. Eksperim. Biol. i. Med.71, 75 (1971)

    Google Scholar 

  4. Alpert, E., Hershberg, R., Schur, P. H., Isselbacher, K. J.: Alpha fetoprotein in human hepatoma: improved detection in serum and quantitative studies using a new sensitive technique. Gastroenterology61, 137 (1971)

    PubMed  Google Scholar 

  5. Alpert, E., Starzl, T. E., Schur, P. H., Isselbacher, K. J.: Serum alpha-fetoprotein in hepatoma patients after liver transplantation. Gastroenterology61, 144 (1971)

    PubMed  Google Scholar 

  6. Avrameas, S., Ternynck, T.: Biologically active water insoluble polymers. I. Their use for isolation of antigens and antibodies. J. biol. Chem.242, 1651 (1967)

    PubMed  Google Scholar 

  7. Beisenherz, G., Boltze, H. J., Bücher, Th., Czok, R., Garbade, K. H., Meyer-Arendt, E., Pfleiderer, G.: Diphosphofructose-Aldolase, Diphosphoglyceraldehyd-dehydrogenase, Milchsäure-dehydrogenase, Glycerophosphat-dehydrogenase und Pyruvatkinase aus Kaninchenmuskulatur in einem Arbeitsgang. Z. Naturforsch.8b, 555 (1953)

    Google Scholar 

  8. Bode, Ch., Goebell, H., Stähler, E.: Zur Eliminierung von Trübungsfehlern bei der Eiweißbestimmung mit der Biuretmethode. Z. klin. Chem.6, 418 (1968)

    Google Scholar 

  9. Buffe, D., Rimbaut, C., Burtin, P.: Presence of a tissue protein, α2-H-globulin, in the serum of patients with neoplastic diseases. Int. J. Cancer3, 850 (1968)

    PubMed  Google Scholar 

  10. De Nechaud, B., Economopoulos, P., Uriel, J.: Fréquence d'apparition des foetoprotéines dans le sérum de malades atteints d'hépatopathies diverses. Presse méd.77, 1954 (1969)

    Google Scholar 

  11. Dufour, D., Barrette, D., Tremblay, A.: Localisation de l'alpha-foeto-protéine du liquide amniotique dans les cellules de la lingée érythroblastique du foie et du sang embryonnaire du rat. Rev. Immunol. (Paris)33, 315 (1969)

    Google Scholar 

  12. Engelgardt, N. V., Goussev, A. I., Shipova, L. Y., Abelev, G. I.: Immunofluorescent study of a-foetoprotein (afp) in liver and liver tumours. I. Technique of afp-localisation in tissue sections. Int. J. Cancer7, 198 (1971)

    PubMed  Google Scholar 

  13. Engelgardt, N. V., Shipova, L. Y., Goussev, A. I., Yazova, A. K., Ter-Grigorova, E. N.: Detection of αF-globulin on slices of the liver of human embryo and neonate mice with the aid of fluorescent agents. Biull. Eksperim. Biol. i. Med.67, 62 (1969)

    Google Scholar 

  14. Gitlin, D., Boesman, M.: Serum alpha-fetoprotein, albumin and globulin in the human conceptus. J. clin. Invest.45, 1826 (1966)

    PubMed  Google Scholar 

  15. Grabar, P.: Introductory remarks on foetal proteins and theirs reappearance in tumors. Prot. Biol. Fluids18, 201 (1970)

    Google Scholar 

  16. Grabar, P.: Distinction des origines de tumeurs á l'áide de méthodes immunologiques. C. R. Acad. Sci. (Paris)275, 2447 (1972)

    Google Scholar 

  17. Grabar, P., Williams, C. A.: Méthode permettant l'étude conjugée des propriétés électrophorétiques et immunochimiques d'un mélange de protéines; application ou sérum sanguin. Biochim. biophys. Acta (Amst.)10, 193 (1953)

    PubMed  Google Scholar 

  18. Häkkinen, I., Viikari, S.: Occurrence of fetal sulphoglycoprotein antigen in the gastric juice of patients with gastric disease. Ann. Surg.169, 277 (1969)

    PubMed  Google Scholar 

  19. Huebner, R. J., Kelloff, G. J.: Group-specific (gs) antigen expression of the C-type RNA tumor virus genome during embryogenesis: implications for ontogenesis and oncogenesis. Proc. nat. Acad. Sci. (Wsch.)67, 366 (1970)

    PubMed  Google Scholar 

  20. Kabat, E. A., Mayer, M. M.: Experimental immunochemistry. p. 122 und 798. Springfield/III.: Thomas Publ. 1961

    Google Scholar 

  21. Kekomäki, M., Seppälä, M., Ehnholm, L., Schwartz, A. L., Raivio, K.: Perfusion of isolated human fetal liver: synthesis and release of α-fetoprotein and albumin. Int. J. Cancer8, 250 (1971)

    PubMed  Google Scholar 

  22. Laurence, D. J. R., Stevens, U., Bettelheim, R., Darcy, D., Leese, C., Tuberville, C., Alexander, P., Johns, E. W., Munro Neville, A.: Role of plasma carcinoembryonic antigen in diagnosis of gastrointestinal, mammary and bronchial carcinoma. Brit. med. J.1972 III, 605

    Google Scholar 

  23. Lehmann, F.-G.: Kristallisation von α1-Foetoprotein aus dem Plasma eines Patienten mit primärem Leberzellkarzinom. Klin. Wschr.49, 609 (1971)

    PubMed  Google Scholar 

  24. Lehmann, F.-G.: Glutamate dehydrogenase from human liver. III. Antibody-binding sites and properties of the antigen-antibody complex. Biochim. biophys (Amst.)235, 259 (1971)

    PubMed  Google Scholar 

  25. Lehmann, F.-G.: Glutamatdehydrogenase aus menschlicher Leber. VI. Glutamatdehydrogenase in primären Leberzellkarcinomen. Klin. Wschr.49, 1065 (1971)

    PubMed  Google Scholar 

  26. Lehmann, F.-G., Lehmann, D.: Isolierung und Kristallisation von α1-Foetoprotein aus einem primären Leberzellkarzinom. Z. klin. Chem.9, 309 (1971)

    Google Scholar 

  27. Lehmann, F.-G., Lehmann, D.: Neue immunologische Techniken und quantitative Bestimmung von α1-Foetoprotein in der Tumordiagnostik. Verh. dtsch. Ges. inn. Med.78, 841 (1972)

    PubMed  Google Scholar 

  28. Lehmann, F.-G., Lehmann, D.: Vergleich verschiedener Methoden zum serologischen Nachweis von α1-Foetoprotein im Serum. Z. klin. Chem.11, 339 (1973)

    Google Scholar 

  29. Lehmann, F.-G., Lehmann, D., Martini, G. A.: α1-Foetoprotein. Isolierung und Kristallisation aus menschlichem Plasma. Clin. chim. Acta33, 197 (1971)

    PubMed  Google Scholar 

  30. Linder, E., Seppälä, M.: Localization of the alpha-foetoprotein in the human fetus and plazenta. Acta. path. microbiol. scand.73, 565 (1968)

    PubMed  Google Scholar 

  31. Mancini, G., Carbonara, O., Heremans, J. F.: Immunochemical quantification of antigens by single radial immunodiffusion. Int. J. Immunochem.2, 235 (1965)

    Google Scholar 

  32. Masseyeff, R., Basteris, B., Leblanc, L.: Use of the alpha-fetoprotein test for the diagnosis of primary liver cancer. Prot. Biol. Fluids18, 217 (1970)

    Google Scholar 

  33. Masseyeff, R., Bonet. C., Lafont, J., Delmont, J.: Interêt en hépatologie du dosage radio-immunologique de traces d'alpha-foetoprotéine. 9. Int. Kongress für Gastroenterologie, Paris, 6. Juli 1972, abstract: Arch. Mal. Appar. dig.61, 17c (1972)

  34. Masseyeff, R., Sankale, M., Onde, M., Menye, A., Camain, R., Quenum, C., Maydat, L., Mattern, P., Ancelle, P., Leblanc, L.: Valeur de la recherche de l'alpha-foetoprotéine sérique pour le diagnostic du cancer primitif du foie. Bull. Soc. méd. Afr. noire Langue franc.13, 537 (1968)

    Google Scholar 

  35. Nathanson, L., Fishman, W. H.: New observations on the Regan-isoenzyme of alkaline phosphatase in cancer patients. Cancer (Philad.)27, 1388 (1971)

    PubMed  Google Scholar 

  36. Nishi, S.: Isolation and characterization of human alpha-globulin from the sera of fetuses and a hepatoma patient. Cancer Res.30, 2507 (1970)

    PubMed  Google Scholar 

  37. Nishi, S., Hirai, H.: Purification of human, dog and rabbit α-fetoprotein by immunoabsorbents of Sepharose coupled with anti-human-α-fetoprotein. Biochim. biophys. Acta (Amst.)278, 293 (1972)

    PubMed  Google Scholar 

  38. Nishioka, M., Ibata, T., Okita, K., Harada, T., Fujita, T.: Localization of α1-fetoprotein in hepatoma tissues by immunofluorescence. Cancer Res.32, 162 (1972)

    PubMed  Google Scholar 

  39. Nunez, E., Engelmann, F., Benassay, G., Jayle, M.-F.: Identification et purification préliminaire de la foetoprotéine liant les oestrogènes dans le sérum de rats nouveaunés. C. R. Acad. Sci. (Paris)273, 242 (1971)

    Google Scholar 

  40. O'Conor, G. T., Tatarinov, Y. S., Abelev, G. I., Uriel, J.: A collaborative study for the evaluation of a serological test for primary liver cancer. Cancer (Philad.)25, 1091 (1970)

    PubMed  Google Scholar 

  41. Ouchterlony, Ö.: Diffusion-in-gel methods for immunological analysis. Progr. Allergy5, 1 (1958)

    Google Scholar 

  42. Piazzi, S. E.: A simple method for preliminary immunodiffusion test of antigen-antibody-systems having unknown ratios of reaction. Analyt. Biochem.27, 281 (1969)

    PubMed  Google Scholar 

  43. Pierce, G.: Differentiation of normal and malignant cell. Fed. Proc.29, 1248 (1970)

    PubMed  Google Scholar 

  44. Pfleiderer, G., Linke, R., Reinhardt, G.: On the evolution of endopeptidases. VIII. Cross reaction of trypsins and chymotrypsins of different species. Comp. Biochem. Physiol.33, 955 (1970)

    PubMed  Google Scholar 

  45. Purtilo, D. Z., Yunis, E. J.: α-Fetoprotein: Its immunofluorescent localization in human fetal liver and hepatoma. Lab. Invest.25, 291 (1971)

    PubMed  Google Scholar 

  46. Purves, L. R., Bersohn, I., Geddes, E. W.: Serum alpha-fetoprotein and primary cancer of the liver in man. Cancer (Philad.)25, 1261 (1970)

    PubMed  Google Scholar 

  47. Purves, L. R., Purves, M.: Serum alpha-fetoprotein. VI. The radio-immunoassay. Evidence for the presence of AFP in the serum of normal people and during pregnancy. S. Afr. med. J.46, 1290 (1972)

    PubMed  Google Scholar 

  48. Rajewski, K., Rottländer, E., Peltre, G., Müller, B.: The immune response to a hybrid protein molecule—Specificity of secundary stimulation and of tolerance induction. J. exp. Med.126, 581 (1967)

    PubMed  Google Scholar 

  49. Reynoso, G., Chu, T. M., Holyoke, D., Cohen, E., Nemoto, T., Wang, J. J., Chuang, J., Guinan, P., Murphy, G. P.: Carcinoembryonic antigen in patients with different cancers. J. Amer. med. Ass.220, 361 (1972)

    Google Scholar 

  50. Ruoslahti, E., Seppälä, M.: Studies of carcino-fetal proteins. Physical and chemical properties of human alpha-fetoprotein. Int. J. Cancer7, 218 (1971)

    PubMed  Google Scholar 

  51. Ruoslahti, E., Seppälä, M.: Studies on carcino-fetal proteins. III. Development of a radio-immunoassay for α-fetoprotein. Demonstration of α-fetoprotein in serum of healthy human adults. Int. J. Cancer8, 374 (1971)

    PubMed  Google Scholar 

  52. Ruoslahti, E., Seppälä, M., Pihko, H., Vuopio, P.: Studies of carcino-fetal proteins. II. Biochemical comparison of α1-fetoprotein from human fetuses and patients with hepatocellular cancer. Int. J. Cancer8, 283 (1971)

    PubMed  Google Scholar 

  53. Scheidegger, J. J.: Une micro-méthode de l'immunoélectrophorèse. Int. Arch. Allergy7, 103 (1955)

    PubMed  Google Scholar 

  54. Stanislawski-Birencwajg, M., Uriel, J., Grabar, P.: Association of embryonic antigens with experimental induced hepatic lesions in the rat. Cancer Res.27, 1990 (1967)

    PubMed  Google Scholar 

  55. Tal, Ch., Halpern, M.: Presence of serologically distinct protein in serum of cancer patients and pregnant women. Israel J. Sci.6, 708 (1970)

    Google Scholar 

  56. Tatarinov, Y. S.: Detection of embryospecific alpha-globulin in the blood sera of patients with primary liver cancer. Vop. med. Khim.10, 90 (1964)

    Google Scholar 

  57. Tatarinov, Y. S., Assecritova, I. V., Masyukivich, V. N., Perova, S. D.: Immunochemical test on embryospecific alpha and beta globulins in differential diagnosis of primary liver cancer. Ther. Arch. (U.S.S.R.)8, 43 (1967)

    Google Scholar 

  58. Trouillas, P.: Immunologie des tumeurs cérébrales: l'antigène carcinofoetal glial. Ann. Inst. Pasteur122, 819 (1972)

    Google Scholar 

  59. Uriel, J.: Transitory liver antigens and primary hepatoma in man and rat. Path. et Biol.17, 877 (1969)

    Google Scholar 

  60. Uriel, J.: Transitory liver antigens and primary hepatoma. Prot. Biol. Fluids18, 211 (1970)

    Google Scholar 

  61. Uriel, J., De Nechaud, B., Dupiers, M.: Estrogen-binding properties of rat, mouse and man fetospecific serum proteins, demonstration by immuno-auroradiographic methods. Biochem. biophys. Res. Commun.46, 1175 (1972)

    PubMed  Google Scholar 

  62. Furth, R. van, Adinolfi, M.: In vitro synthesis of the foetal alpha-1-globulin in man. Nature (Lond.)222, 1296 (1969)

    PubMed  Google Scholar 

  63. Wada, T., Anzai, T., Yachi, A., Takahashi, A., Sakamoto, S.: Incidences of three different fetal proteins in sera of patients with primary hepatoma. Prot. Biol. Fluids18, 221 (1970)

    Google Scholar 

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V. Mitteilung über α1-Foetoprotein. I.: Clin. chim. acta33, 197 (1971); II.: Z. klin. Chem. u. klin. Biochem.9, 309 (1971); III.: Z. klin. Chem. u. klin. Biochem.11, 339 (1973); IV.: Klin. Wschr.52, 216 (1974).

Über Teilergebnisse wurde auf dem 7. Symposium der European Association for the Study of the Liver, Arnheim, 7. Sept. 1972 (abstract: Digestion6, 249 (1972) und auf der 27. Tagung der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten, Frankfurt, 7. Okt. 1972 berichtet.

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Lehmann, F.G., Lehmann, D. α1-Foetoprotein in malignen Tumoren. Klin Wochenschr 52, 222–232 (1974). https://doi.org/10.1007/BF01468595

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