Tumor Markers in Gynecologic Malignancies

  • John R. van Nagell
Part of the Cancer Treatment and Research book series (CTAR, volume 10)


For practical purposes, a tumor marker can be defined as a substance which is selectively produced by a tumor and then released into the circulation in detectable amounts. An ideal marker is tumor-specific, i.e. produced only by tumor cells. Elevated serum levels of such a marker would, therefore, indicate the presence of a tumor and its absence following therapy would signify the lack of viable malignant cells. Unfortunately, no truly tumor-specific markers have been detected in gynecologic cancers. Rather, several nonspecific oncofetal and hormonal markers have been shown to be quantitatively increased both in the tumor tissue and sera of patients with gynecologic malignancies. Also, a small number of tumor-associated antigens have been described in ovarian and cervical cancers. Although elevated plasma and tumor concentrations of these biochemical markers have been confirmed by a number of investigators, there remains considerable skepticism concerning their usefullness in clinical medicine.


Cervical Cancer Carcinoembryonic Antigen Gynecologic Cancer Gynecologic Malignancy Embryonal Cell Carcinoma 
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. 1.
    Gold P, Freedman SO: Demonstration of tumor specific antigens in human colonic carcinoma by immunological tolerance and absorption techniques. J Exp Med 121:439–462, 1965.PubMedCrossRefGoogle Scholar
  2. 2.
    Krupey J, Gold P, Freedman SO: Purification and characterisation of carcinoembryonic antigens of the human digestive system. Nature (London) 215:67–68, 1967.CrossRefGoogle Scholar
  3. 3.
    Khoo SK, MacKay EV: Carcinoembryonic antigen in cancer of the female reproductive system. Sequential levels and effects of treatment. Aust New Zealand J Obstet Gynecol 13:1–7, 1973.CrossRefGoogle Scholar
  4. 4.
    DiSaia PJ, Haverback BJ, Morrow CP: Carcinoembryonic antigen in patients with gynecologic malignancies. Am J Obstet Gynecol 121:159–166, 1975.PubMedGoogle Scholar
  5. 5.
    van Nagell JR, Donaldson ES, Wood EG, Sharkey RM, Goldenberg DM: The prognostic significance of carcinoembryonic antigen in the plasma and tumors of patients with endometrial adenocarcinoma. Am J Obstet Gynecol 128:308–313, 1977.PubMedGoogle Scholar
  6. 6.
    van Nagell JR, Donaldson ES, Gay EC, Sharkey RM, Rayburn P, Goldenberg DM: Carcinoembryonic antigen in ovarian epithelial cystadenocarcinomas: Prognostic value of serial plasma determinations. Cancer 41:2335–2340, 1978.PubMedCrossRefGoogle Scholar
  7. 7.
    van Nagell JR, Donaldson ES, Wood EC, Goldenberg DM: The clinical significance of carcinoembryonic antigen in the plasma and tumors of patients with gynecologic malignancies. Cancer 42:1527–1532, 1978.PubMedCrossRefGoogle Scholar
  8. 8.
    van Nagell JR, Donaldson ES, Gay EC, Rayburn P, Powell DF, Goldenberg DM: Carcinoembryonic antigen in carcinoma of the uterine cervix. 1. The prognostic value of serial plasma determinations. Cancer 42:2428–2434, 1978.PubMedCrossRefGoogle Scholar
  9. 9.
    van Nagell JR, Donaldson ES, Gay EC, Hudson S, Sharkey RM, Primus FJ, Powell DF, Goldenberg DM: Carcinoembryonic antigen in carcinoma of the uterine cervix. 2. Tissue localization and correlation with plasma antigen concentration. Cancer 44:944–948, 1979.PubMedCrossRefGoogle Scholar
  10. 10.
    Goldenberg DM, Sharkey RM, Primus FJ: Carcinoembryonic antigen in histopathology: Immunoperoxidase staining of conventional tissue sections. J Natl Cancer Inst 57:11–21, 1976.PubMedGoogle Scholar
  11. 11.
    van Nagell JR, Meeker W, Parker JC, Harralson JD: Carcinoembryonic antigen in patients with gynecologic malignancy. Cancer 35:1372–1376, 1975.PubMedCrossRefGoogle Scholar
  12. 12.
    Shuster J, Silverman M, Gold P: Metabolism of human carcinoembryonic antigen in xenogeneic animals. Cancer Res 33:65–68, 1973.PubMedGoogle Scholar
  13. 13.
    Lurie BB, Oweinstein MS, Zamcheck N: Elevated carcinoembryonic antigen levels and biliary tract obstruction. JAMA 233:326–330, 1975.PubMedCrossRefGoogle Scholar
  14. 14.
    Wahlstrom T, Lindgren J, Korhonen M, Seppala M: Distinction between endocervical and endometrial adenocarcinoma with immunoperoxidase staining of carcinoembryonic antigen in routine histological tissue specimens. Lancet 24:1159–1160, 1979.CrossRefGoogle Scholar
  15. 15.
    Barrelet V, Mach J: Variations of the carcinoembryonic antigen level in the plasma of patients with gynecologic cancers during therapy. Am J Obstet Gynecol 121:164–168, 1975.Google Scholar
  16. 16.
    Donaldson ES, van Nagell JR, Wood EG, Pletsch Q, Goldenberg DM: Carcinoembryonic antigen in patients treated with radiation therapy for invasive squamous cell carcinoma of the uterine cervix. Am J Roentgenol 127:829–831, 1976.Google Scholar
  17. 17.
    Gold P, Krupey J, Ansari H: Position of the carcinoembryonic antigen of the human digestive system in ultrastructure of tumor cell surface. J Natl Cancer Inst 45:219–225, 1970.PubMedGoogle Scholar
  18. 18.
    Tappeiner G, Denk H, Eckerstorfer R, Holzner JH: Vergleichende Untersuchungen über Auftreten und Lokalisation des carcinoembryonalen Antigens (CEA) und eines normalen perchlorsaure-extrahierbaren Dickdarmschleimhautantigens (NC) in Carcinomen und Polypes des Dickdarmes. Virchows Arch Path Anat 360:129–140, 1973.Google Scholar
  19. 19.
    Primus FJ, Wang RH, Sharkey RM, Goldenberg DM: Detection of carcinoembryonic antigen in tissue sections by immunoperoxidase. J Immunol Methods 8:267–276, 1975.PubMedCrossRefGoogle Scholar
  20. 20.
    Huitric E, Laumonier R, Burtin P, Kleist S, von Chevanel G: An optical and ultrastructural study of the localization of carcinoembryonic antigen (CEA) in normal and cancerous human rectocolonic mucosa. Lab Invest 34:97–107, 1976.PubMedGoogle Scholar
  21. 21.
    Goldenberg DM, DeLand F, Kim E, Bennett S, Primus FJ, van Nagell JR, Estes N, De Simone PJ, Rayburn P: Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med 298:1384–1388, 1978.PubMedCrossRefGoogle Scholar
  22. 22.
    van Nagell JR, Kim E, Casper S, Primus FJ, Bennett S, DeLand FH, Goldenberg DM: Radioimmunodetection of primary and metastatic ovarian cancer using radiolabeled antibodies to carcinoembryonic antigen. Cancer Res 40:502–506, 1980.PubMedGoogle Scholar
  23. 23.
    Vaitukaitis JL, Braunstein GP, Ross GT: A radioimmunoassay which specifically measures human chorionic gonadotropin in the presence of human luteinizing hormone. Am J Obstet Gynecol 113:751–756, 1972.PubMedGoogle Scholar
  24. 24.
    Li MC, Hertz R, Bergenstral DM: Therapy of choriocarcinoma and related trophoblastic tumors with folic acid and purine antagonists. N Engl J Med 259:66–70, 1958.PubMedCrossRefGoogle Scholar
  25. 25.
    Hertz R, Lewis J, Lipsett MB: Five years’ experience with the chemotherapy of metastatic choriocarcinoma and related trophoblastic tumors in women. Am J Obstet Gynecol 82: 631–637, 1961.PubMedGoogle Scholar
  26. 26.
    Pattillo RA, Grey GO: The establishment of a cell line of human hormone synthesizing trophoblastic cells in vitro. Cancer Res 24:1231–1236, 1968.Google Scholar
  27. 27.
    Kanabus J, Braunstein GD, Emry PK, DiSaia PJ, Wade ME: Kinetics of growth and ectopic production of human chorionic gonadotropin by an ovarian cystadenocarcinoma cell line maintained in vitro. Cancer Res 38:765–770, 1978.PubMedGoogle Scholar
  28. 28.
    Yorde DE, Hussa RO, Garancis JC, Pattillo RA: Immunocytochemical localization of human choriogonadotropin in human malignant trophoblast: Model for human choriogonadotropin secretion. Lab Invest 40:391–398, 1979.PubMedGoogle Scholar
  29. 29.
    Hammond CB, Weed JC, Currie JL: The role of operation in the current therapy of gestational trophoblastic disease. Am J Obstet Gynecol 136:844–858, 1980.PubMedGoogle Scholar
  30. 30.
    Donaldson ES, van Nagell JR, Pursell S, Kashmiri R, Meeker WR, van de Voorde J, Gay EC: Multiple Biochemical markers in patients with gynecologic malignancies. Cancer 45:948–953, 1980.PubMedCrossRefGoogle Scholar
  31. 31.
    Rutanen EM, Seppala M: The hCG-subunit radioimmunoassay in non-trophoblastic gynecologic tumors. Cancer 41:692–696, 1978.PubMedCrossRefGoogle Scholar
  32. 32.
    Kurman RJ, Norris HJ: Embryonal carcinoma of the ovary: A clinico-pathological entity distinct from endodermal sinus tumor resembling embryonal carcinoma of the adult testes. Cancer 38:2420–2433, 1976.PubMedCrossRefGoogle Scholar
  33. 33.
    Kohler PO, Bridson WE, Hammond J, Weintraub B, Kirschner MA, Van Thiel DH: Clonal lines of human choriocarcinoma cells in culture. In: Diczfalusy E, ed.: Karolinska Symposia on Research Methods in Reproductive Endocrinology, Denmark, 1971, Bogtry Keriet Forum, pp. 137–153.Google Scholar
  34. 34.
    Goldenberg DM, Kim E, DeLand FH, van Nagell JR, Javadpour N: Clinical radioimmunodetection of cancer using radioactive antibodies to human chorionic gonadotropin. Science 208:1284–1286, 1980.PubMedCrossRefGoogle Scholar
  35. 35.
    Ruoslahti E, Seppala M: Studies of carcino- fetal proteins. III. Development of a radioimmunoassay for α-fetoprotein in serum of healthy human adults. Int J Cancer 8:374–383, 1971.PubMedCrossRefGoogle Scholar
  36. 36.
    Abelev GI: Study of the antigenic structure of tumors. Acta Un Intern Cancer 19:80–92, 1963.Google Scholar
  37. 37.
    Seppala M, Ruoslahti E: Alpha-fetoprotein: Physiology and pathology during pregnancy and application to antenatal diagnosis. J Perinat Med 1:104–113, 1973.PubMedCrossRefGoogle Scholar
  38. 38.
    Tatarinov JS: Presence of embryonal α-globulin in the serum of a patient with primary hepatocellular carcinoma. Vop Med Khim 1:90–91, 1964.Google Scholar
  39. 39.
    Talerman A, Haije WG, Beggerman L: Serum alpha-fetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk-sac) tumor and mixed germ cell tumor of the ovary. Cancer 41:272–278, 1978.PubMedCrossRefGoogle Scholar
  40. 40.
    Kurman RJ, Norris HJ: Endodermal sinus tumor of the ovary. Cancer 38:2404–2419, 1976.PubMedCrossRefGoogle Scholar
  41. 41.
    Gallion H, van Nagell JR, Powell DF, Donaldson ES, Hanson M: Therapy of endodermal sinus tumor of the ovary. Am J Obstet Gynecol 135:447–451, 1979.PubMedGoogle Scholar
  42. 42.
    Sell A, Sogaard H, Horgaard-Pedersen B: Serum alpha feto-protein as a marker for the effect of post-operative radiation therapy and/or chemotherapy in eight cases of ovarian endodermal sinus tumour. Int J Cancer 18:574–580, 1976.PubMedCrossRefGoogle Scholar
  43. 43.
    Goldenberg DM, Kim E, DeLand F, Spermulli E, Nelson MO, Cockerman JP, Primus FJ, Corgan RL, Alpert E: Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein. Cancer 45:2500–2505, 1980.PubMedCrossRefGoogle Scholar
  44. 44.
    Witebsky E, Rose NR, Schulman S: Studies of normal and malignant tissue antigens. Cancer Res 16:831–841, 1956.PubMedGoogle Scholar
  45. 45.
    Bhattacharya M, Barlow JJ: Immunologic studies of human serous cystadenocarcinoma of ovary. Cancer 31:588–595, 1972.CrossRefGoogle Scholar
  46. 46.
    Bhattacharya M, Barlow JJ: A tumor-associated antigen from cystadenocarcinomas of the ovary. Natl Cancer Inst Monog 42:25–32, 1975.Google Scholar
  47. 47.
    Bhattacharya M, Barlow JJ: Tumor markers for ovarian cancer. Int Adv Surg Oncol 2: 155–176, 1979.PubMedGoogle Scholar
  48. 48.
    Bhattacharya M, Barlow JJ: Ovarian tumor antigens. Cancer 42:1616–1620, 1978.PubMedCrossRefGoogle Scholar
  49. 49.
    Knauf S, Urbach EI: Ovarian tumor-specific antigens. Am J Obstet Gynecol 119:966–970, 1974.PubMedGoogle Scholar
  50. 50.
    Knauf S, Urbach GI: Purification of human ovarian tumor-associated antigen and demonstration of circulating tumor-antigen in patients with advanced ovarian malignancy. Am J Obstet Gynecol 127:705–711, 1977.PubMedGoogle Scholar
  51. 51.
    Knauf S, Urbach GI: The development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma. Am J Obstet Gynecol 131:780–786, 1978.PubMedGoogle Scholar
  52. 52.
    Kato H, Torigoe T: Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma. Cancer 40:1621–1628, 1977.PubMedCrossRefGoogle Scholar
  53. 53.
    Kato H, Miyauchi F, Morioka H, Fujino T, Torigoe T: Tumor antigen of human cervical squamous cell carcinoma. Correlation of circulating levels with disease progress. Cancer 43:585–590, 1979.PubMedCrossRefGoogle Scholar
  54. 54.
    Nakane PK, Pierce GB: Enzyme labeled antibodies: Preparation and application for the localization of antigens. J Histochem Cytochem 14:929–931, 1966.PubMedCrossRefGoogle Scholar
  55. 55.
    Primus FJ, Sharkey RM, Hansen HJ, Goldenberg DM: Immunoperoxidase detection of carcinoembryonic antigen: An overview. Cancer 42:1540–1545, 1978.PubMedCrossRefGoogle Scholar
  56. 56.
    Pressman D, Koringold L: The in vivo localization of anti-Wagner osteogenic sarcoma antibodies. Cancer 6:619–623, 1953.PubMedCrossRefGoogle Scholar
  57. 57.
    Spar JL, Bale WF, Marrack D, Dewey WC, McCardle RJ, Harper PV: Labeled antibodies to human fibrinogen. Diagnostic studies and therapeutic trials. Cancer 20:865–870, 1967.PubMedCrossRefGoogle Scholar
  58. 58.
    Ghose T, Norvell ST, Guclu A, Bodurtha A, Tai J, MacDonald AS: Immunochemotherapy of malignant melanoma with chlorambucil-bound antimelanoma globulins and preliminary results in patients with disseminated disease. J Natl Cancer Inst 58:845–852, 1977.PubMedGoogle Scholar
  59. 59.
    Harwitz E, Schecter B, Arnon R, Sela M: Binding of anti-tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastases. In vitro and in vivo studies with Lewis lung carcinoma. Int J Cancer 24:461–470, 1979.CrossRefGoogle Scholar
  60. 60.
    Latif ZA, Lozzio BB, Wust CJ, Krauss S, Aggio MC: Evaluation of drug antibody conjugates in the treatment of human myelosarcomas transplanted in nude mice. Cancer 45:1326–1333, 1980.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers, Boston 1983

Authors and Affiliations

  • John R. van Nagell

There are no affiliations available

Personalised recommendations