Skip to main content
SpringerLink
Log in

Recent Advances in Understanding the Immunobiology of Gestational Trophoblastic Disease

A Review

  • Chapter
Cellular Biology and Pharmacology of the Placenta

Part of the book series: Trophoblast Research ((TR))

  • 29 Accesses

Abstract

Gestational trophoblastic disease, including hydatidiform mole, invasive mole, and choriocarcinoma, comprise a group of interrelated diseases which arise from pregnancy and have varying potentials for local invasion and distant spread. It is now well established that hydatidiform mole may precede the development of persistent gestational trophoblastic tumors including gestational choriocarcinoma (Bagshawe, 1969; Goldstein and Berkowitz, 1982). The results of clinical management of molar pregnancy and gestational trophoblastic tumors has improved considerably over the past three decades due to advances in understanding of the pathology, natural history, and endocrinology of these trophoblastic diseases. In 1956, Li et al. inaugurated a new era in the therapy of gestational choriocarcinoma when they reported curing three women with metastases by treatment with methotrexate. Gestational trophoblastic tumors are now known to be curable with chemotherapy even in the presence of widely metastatic disease. The effective treatment of trophoblastic tumors with chemotherapy represents one of the most dramatic successes in the management of human malignancy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson, D.J., Adams, P.H., Hamilton, M.S., and Alexander, N.J. (1983) Antisperm antibodies in mouse vasectomy sera react with embryonal teratocarcinoma. J. Immunol. 131, 2908–2912.

    CAS  PubMed  Google Scholar 

  • Anderson, D.J. and Berkowitz, R.S. (1985) Gamma-interferon enhances expression of Class I MHC antigens in the weakly H LA-positive human choriocarcinoma cell line Be Wo but does not induce MHC expression in the HLA-negative choriocarcinoma cell line Jar. J. Immunol. 135, 2498–2501.

    CAS  PubMed  Google Scholar 

  • Bagshawe, K.D. (1969) Choriocarcinoma. Edward Arnold, Ltd., London.

    Google Scholar 

  • Bast, R.C., Jr., Feeney, M., Lazarus, H., Nadler, L.M., Colvin, R.B., and Knapp, R.C. (1981) Reactivity of a monoclonal antibody with human ovarian carcinoma. J. Clin. Invest. 68, 1331–1337.

    Article  PubMed Central  PubMed  Google Scholar 

  • Berkowitz, R.S. and Goldstein, D.P. (1981) Pathogenesis of gestational trophoblastic neoplasms. Pathobiol. Ann. 11, 391–411.

    CAS  Google Scholar 

  • Berkowitz, R.S., Hornig-Rohan, J., Martin-Allosco, S., Klein, S., Goldstein, D.P., Bast, R.C., Jr., and DeWolf, W.C. (1981) HLA antigen frequency distribution in patients with gestational choriocarcinoma and their husbands. Placenta Suppl. 3, 263–267.

    CAS  PubMed  Google Scholar 

  • Berkowitz, R.S., Mostoufizadeh, M., Kabawat, S.E., Goldstein, D.P., and Driscoll, S.G. (1982a) Immunopathologic study of the implantation site in molar pregnancy. Am. J. Obstet. Gynecol. 144, 925–930.

    CAS  PubMed  Google Scholar 

  • Berkowitz, R.S., Sandstrom, M., Goldstein, D.P., and Driscoll, S.G. (1982b) 45, X Complete hydatidiform mole. Gynecol. Oncol. 14, 279–283.

    Google Scholar 

  • Berkowitz, R.S., Anderson, D.J., Hunter, N.J., and Goldstein, D.P. (1983a) Distribution of major histocompatibility (HLA) antigens in chorionic villi of molar pregnancy. Am. J. Obstet. Gynecol. 146, 221–222.

    CAS  PubMed  Google Scholar 

  • Berkowitz, R., Kabawat, S., Lazarus, H., Colvin, R., Knapp, R., and Bast, R.C., Jr. (1983b) Comparison of a rabbit heteroantiserum and a murine monoclonal antibody raised against a human epithelial ovarian carcinoma cell line. Am. J. Obstet. Gynecol. 146, 607–612.

    CAS  PubMed  Google Scholar 

  • Berkowitz, R.S., Lahey, S.J., Rodrick, M.L., Rayner, A.A., Goldstein, D.P., and Steele, G., Jr. (1983c) Circulating immune complex levels in patients with molar pregnancy. Obstet. Gynecol. 61, 165–168.

    CAS  PubMed  Google Scholar 

  • Berkowitz, R.S., Hoch, E.J., Goldstein, D.P., and Anderson, D.J. (1984) Histocompatibility antigens (HLA-A,B,C) are not detectable in molar villous fluid. Gynecol. Oncol. 19, 74–78.

    Article  CAS  PubMed  Google Scholar 

  • Berkowitz, R.S., Alberti, O., Jr., Hunter, N.J., Goldstein, D.P., and Anderson, D.J. (1985a) Localization of stage-specific embryonic antigens in hydatidiform mole, normal placenta and gestational choriocarcinoma. Gynecol. Oncol. 20, 71–77.

    Article  CAS  PubMed  Google Scholar 

  • Berkowitz, R.S., Alexander, N.J., Goldstein, D.P., and Anderson, D.J. (1985b) Reactivity of antihuman sperm monoclonal antibodies with normal placenta, hydatidiform mole and gestational choriocarcinoma. Gynecol. Oncol. 22, 334340.

    Google Scholar 

  • Bernirschke, K. and Driscoll, S.G. (1967) The Pathology of the Human Placenta. Springer-Verlag, New York.

    Google Scholar 

  • Bhan, A.K., Mihm, M.C., Jr., and Dvorak, H.F. (1982) T-cell subsets in allograft rejection: In-situ characterization of T-cell subsets in human skin allografts by the use of monoclonal antibodies. J. Immunol. 129, 1578–1583.

    CAS  PubMed  Google Scholar 

  • Daasch, V.N., Fernsten, P.D., and Metzgar, R.S. (1982) Radioimmune assay studies using a monoclonal antibody to detect an antigen (DU-PAN-2) in the serum and ascites of adenocarcinoma patients. Proc. Am. Assoc. Can. Res. (abstract) p. 1051.

    Google Scholar 

  • Davis, J.R., Surwit, E.A., Garay, J.P., and Fortier, K.J. (1984) Sex assignment in gestational trophoblastic neoplasia. Am. J. Obstet. Gynecol. 148, 722–725.

    Article  CAS  PubMed  Google Scholar 

  • Faulk, W.P. and Temple, A. (1976) Distribution of beta-2 microglobulin and HLA in chorionic villi of human placentae. Nature 262, 799–802.

    Article  CAS  PubMed  Google Scholar 

  • Fisher, R.A., and Lawler, S.D. (1984) Heterozygous complete hydatidiform moles: Do they have a worse prognosis than homozygous complete moles? Lancet 2, 51.

    Article  CAS  PubMed  Google Scholar 

  • Fellous, M., Nir, V., Wallach, D., Merlin, G., Rubenstein, M., and Revel, M. (1982) Interferon dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts. Proc. Natl. Acad. Sci. USA 79, 3082–3086.

    Article  CAS  PubMed  Google Scholar 

  • Fox, N., Damjanov, I., Knowles, B.B., and Solter, D. (1983) Immunohistochemical localization of the mouse stage-specific embryonic antigen I in human tissues and tumors. Canc. Res. 43, 669–678.

    CAS  Google Scholar 

  • Goldstein, D.P. and Berkowitz, R.S. (1982) Gestational Trophoblastic Neoplasms: Clincal Principles of Diagnosis and Management. W.B. Saunders, Philadelpha, PA.

    Google Scholar 

  • Heron, I., Hokland, M., and Berg, K. (1978) Enhanced expression of beta 2microglobulin and HLA antigens on human lymphoid cells by interferon. Proc. Natl. Acad. Sci. USA 77, 6215–6219.

    Article  Google Scholar 

  • Hilkens, J., Baijs, F., Hilgers, J., Hageman, Ph., Calafat, J., Sonnenberg, A., and Van der Valk, M. (1984) Monoclonal antibodies against human milk-fat globule membranes detecting differentiation antigens of the mammary glands and its tumors. Int. J. Canc. 34, 197–206.

    Article  CAS  Google Scholar 

  • Jacobs, P.A., Wilson, C.M., Sprenkle, J.A., Rosenshein, N.B., and Migeon, B.R. (1980) Mechanism of origin of complete hydatidiform moles. Nature (London) 286, 714–716.

    Article  CAS  Google Scholar 

  • Kabawat, S.E., Mostoufi-Zadeh, M., Berkowitz, R.S., D riscoll, S.G., Goldstein, D.P., and Bhan, A.K. (1985) Implantation site in complete molar pregnancy: A study of immunologically competent cells with monoclonal antibodies. Am. J. Obstet. Gynecol. 152, 97–99.

    Article  CAS  PubMed  Google Scholar 

  • Kato, M., Tanaka, K., and Takeuchi, S. (1982) The nature of trophoblastic disease initiated by transplantation into immunosuppressed animals. Am. J. Obstet. Gynecol. 142, 497–505.

    CAS  PubMed  Google Scholar 

  • Kajii, T. and Ohama, K. (1977) Androgenetic origin of hydatidiform mole. Nature (London) 268, 633–634.

    Article  CAS  Google Scholar 

  • Kawata, M., Parnes, J.R., and Herzenberg, L.A. (1984) Transcriptional control of HLA-A,B,C antigen in human placental cytotrophoblast isolated using trophoblast-and HLA-specific monoclonal antibodies and the fluorescence-activated cell sorter. J. Exp. Med. 160, 633–651.

    Article  CAS  PubMed  Google Scholar 

  • Klouda, P.T., Lawler, S.D., and Bagshawe, K.D. (1972) HL-A matings in trophoblastic neoplasia. Tiss. Antigens 2, 280–284.

    Article  CAS  Google Scholar 

  • Kufe, D., Inghirami, G., Abe, M., Hayes, D., Justi-Wheeler, H., and’Schlom, J. (1984) Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma 3, 223–232.

    CAS  Google Scholar 

  • Lahey, S.J., Steele, G., Jr., Berkowitz, R.S., Rodrick, M.L., Ross, D.S., Goldstein, D.P., Zamcheck, N., Wilson, R.E., and Deasy, J.M. (1984a) Identification of material with paternal HLA antigen immunoreactivity from purported circulating immune complexes in patients with gestational trophoblastic neoplasia. J. Nat. Canc. Inst. 72, 983–990.

    CAS  Google Scholar 

  • Lahey, S.J., Steele, G., Jr., Rodrick, M.L., Berkowitz, R.S., Goldstein, D.P., Ross, D.S., Ravikumar, T.S., Wilson, R.E., Byrn, R., Thomas, P., and Zamcheck, N. (1984b) Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia. Canc. 53, 1316–1321.

    Article  CAS  Google Scholar 

  • Lawler, S.D., Klouda, P.T., and Bagshawe, K.D. (1971) The HL-A system in trophoblastic neoplasia. Lancet 2, 834–837.

    Article  CAS  PubMed  Google Scholar 

  • Lawler, S.D., Klouda, P.T., and Bagshawe, K.D. (1974) Immunogenicity of molar pregnancies in the HLA system. Am. J. Obstet. Gynecol. 120, 857–861.

    CAS  PubMed  Google Scholar 

  • Lawler, S.D., Pickthall, V.J., Fisher, R.A., Povery, S., Evans, M.W., and Szulman, A.E. (1979) Genetic studies of complete and partial hydatidiform moles. Lancet 2, 580.

    Article  CAS  PubMed  Google Scholar 

  • Lewis, J.L., Jr., and Terasaki, P.I. (1971) HL-A leukocyte antigen studies in women with gestational trophoblastic neoplasms. Am. J. Obstet. Gynecol. 111, 547552.

    Google Scholar 

  • Li, M.C., Hertz, R., and Spencer, D.B. (1956) Effect of methotrexate therapy on choriocarcinoma and chorioadenoma. Proc. Soc. Exp. Biol. Med. 93, 361–366.

    Article  PubMed  Google Scholar 

  • Loke, Y.W., Whyte, A., and Davies, S.P. (1980) Differential expression of trophoblastspecific membrane antigens by normal and abnormal human placentae and by neoplasms of trophoblastic and non-trophoblastic origin. Int. J. Canc. 25, 459461.

    Google Scholar 

  • Magnani, J., Steplewski, Z., Koprowski, H., and Ginsburg, V. (1983) Identification of the gastrointestinal 9nd pancreatic cancer-associated antigen detected by monoclonal antibody 19–9 in the sera of patients as a mucin. Canc. Res. 43, 5489–5492.

    CAS  Google Scholar 

  • Menge, A.C. and Fleming, C.H. (1978) Detection of sperm antigens on mouse ova and early embryos. Develop. Biol. 63, 111–117.

    Article  CAS  PubMed  Google Scholar 

  • Miotti, S., Aguanno, S., Canevari, S., Diotti, A., Orlandi, R., Sonnion, S., and Colnaghi, M.I. (1985) Biochemical analysis of human cancer-associated antigens defined by murine monoclonal antibodies. Canc. Res. 45, 826–832.

    CAS  Google Scholar 

  • Mittal, K.K., Kachru, R.B., and Brewer, J.I. (1975) The HL-A and ABO antigens in trophoblastic disease. Tissue Antigens 6, 57–69.

    Article  CAS  PubMed  Google Scholar 

  • Morgensen, B., Kissmeyer-Nielsen, F., and Hauge, M. (1969) Histocompatibility antigens on the HL-A locus in gestational choriocarcinoma. Transplant. Proc. 1, 76–80.

    Google Scholar 

  • Pattillo, R.A. and Gey, G.O. (1968) The establishment of a cell-line of human hormone-synthesizing trophoblastic cells in vitro. Canc. Res. 28, 1231–1236.

    CAS  Google Scholar 

  • Pattillo, R.A., Ruckert, A., Hussa, R.O., Bernstein, R., and Delfs, E. (1971) The Jar cell line. Continuous human multihormone production and controls. In Vitro 6, 398.

    Google Scholar 

  • Pattillo, R.A., Sasaki, S., Katayama, K.P., Roesler, M., and Mattingly, R.F. (1981) Genesis of 46, XY hydatidiform mole. Am. J. Obstet. Gynecol. 141, 104–105.

    CAS  PubMed  Google Scholar 

  • Saksela, O., Wahlstrom, T., Lehtovirta, P., Seppala, M., and Vaheri, A. (1981) Presence of alpha 2-macroglobulin in normal but not in malignant human syncytiotrophoblasts. Canc. Res. 41, 2507–2513.

    CAS  Google Scholar 

  • Sasagawa, M., Kajino, T., Kanazawa, K., and Takeuchi, S. (1984) Immunohistochemical study on subpopulations of trophoblasts in normal pregnancy and hydatidiform mole. Proc. Second World Cong. Trophoblastic Neoplasms, abstract, p. 13.

    Google Scholar 

  • Sasaki, S., Katayama, P.K., Roesler, M., Pattillo, R.A., Mattingly, R.F., and Ohkawa, K. (1982) Cytogenetic analysis of choriocarcinoma cell lines. Acta Obstet. Gynecol. Jpn. 34, 2253–2256.

    CAS  Google Scholar 

  • Seppala, M., Wahlstrom, T., and Bohn, H. (1979) Circulating levels and tissue localization of placental protein five (PP5) in pregnancy and trophoblastic disease: Absence of PP5 expression in the malignant trophoblast. Int. J. Canc. 24, 6–10.

    Article  CAS  Google Scholar 

  • Shaw, A.R.E., Dasgupta, M.K., Kovithavongs, T., Johny, K.V., LeRiche, J.L., Dossetor, J.B., and McPherson, T.A. (1979) Humoral and cellular immunity to paternal antigens in trophoblastic neoplasia. Int. J. Canc. 24, 586–593.

    Article  CAS  Google Scholar 

  • Shevinsky, L.H., Knowles, B.B., Damjanov, I., and Solter, D. (1982) Monoclonal antibody to murine embryos define a stage-specific embryonic antigen expressed on mouse embryos and human teratocarcinoma cells. Cell 30, 697705.

    Google Scholar 

  • Solter, D. and Knowles, B.B. (1978) Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1). Proc. Natl. Acad. Sci. USA 75, 5565–5569.

    Article  CAS  PubMed  Google Scholar 

  • Sunderland, C.A., Redman, C.W.G., and Stirrat, G.M. (1981) HLA-A,B,C antigens are expressed on non-villous trophoblast of the early human placenta. J. Immunol. 127, 2614–2615.

    CAS  PubMed  Google Scholar 

  • Sunderland, C.A., Redman, C.W.G., and Stirrat, G.M. (1985) Characterization and localization of HLA antigens on hydatidiform mole. Am. J. Obstet. Gynecol. 151, 130–135.

    Article  CAS  PubMed  Google Scholar 

  • Surti, U., Szulman, A.E., and O’Brien, S. (1979) Complete (classic) hydatidiform mole with 46, XY karyotype of paternal origin. Hum. Genet. 51, 153–155.

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi, S. (1980) Immunology of spontaneous abortion. Am. J. Reprod. Immunol. 1, 23–28.

    Article  CAS  PubMed  Google Scholar 

  • Tomoda, Y., Fuma, M., Saiki, N., Ishizuka, N., and Akaza, T. (1976) Immunologic studies in patients with trophoblastic neoplasia. Am. J. Obstet. Gynecol. 126, 661–667.

    CAS  PubMed  Google Scholar 

  • Trowsdale, J., Travers, P., Bodmer, W.F., and Pattillo, R.A. (1980) Expression of HLA-A,B, and C and beta-2 microglobulin antigens in human choriocarcinoma cell lines. J. Exp. Med. 152, 11S - 17S.

    CAS  PubMed  Google Scholar 

  • Wake, N., Takagi, N., and Sasaki, M. (1978) Androgenesis as a cause of hydatidiform mole. J. Natl. Canc. Inst. 60, 51–53.

    CAS  Google Scholar 

  • Wake, N., Tanaka, K., Chapman, V., Matsui, S., and Sandberg, A.A. (1981) Chromosomes and cellular origin of choriocarcinoma. Canc. Res. 41, 31373143.

    Google Scholar 

  • Wake, N., Seki, T., Fujita, H., Okubo, H., Sakai, K., Okuyama, K., Hayashi, H., Shiina, H.J., Sato, H., Kuroda, M., and Ichinoe, K. (1984) Malignant potential of homozygous and heterozygous complete moles. Canc. Res. 44, 1226–1230.

    CAS  Google Scholar 

  • Yamashita, K., Wake, N., Araki, T., Ichinoe, K., and Makoto, K. (1979) Human lymphocyte antigen expression in hydatidiform mole: Androgenesis following fertilization by a haploid sperm. Am. J. Obstet. Gynecol. 135, 597–600.

    CAS  PubMed  Google Scholar 

  • Yamashita, K., Ishikawa, M., Shimizu, T., and Kuroda, M. (1981a) HLA-antigens in husband-wife pairs with trophoblastic tumor. Gyneco. Oncol. 12, 68–74.

    Article  CAS  Google Scholar 

  • Yamashita, K., Wake, N., Araki, T., Ichinoe, K., and Kuroda, M. (1981b) A further HLA study of hydatidiform moles. Gynecol. Oncol. 11, 23–28.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Fearing Research Laboratory New England Trophoblastic Disease Center Division of Gynecologic Oncology Brigham and Women’s Hospital Department of Obstetrics and Gynecology and Pathology, Harvard Medical School, Boston, Massachusetts, USA

    Ross S. Berkowitz, Donald P. Goldstein & Deborah J. Anderson

Authors
  1. Ross S. Berkowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donald P. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Deborah J. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Rochester Medical Center, Rochester, New York, USA

    Richard K. Miller  & Henry A. Thiede  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Springer Science+Business Media New York

About this chapter

Cite this chapter

Berkowitz, R.S., Goldstein, D.P., Anderson, D.J. (1987). Recent Advances in Understanding the Immunobiology of Gestational Trophoblastic Disease. In: Miller, R.K., Thiede, H.A. (eds) Cellular Biology and Pharmacology of the Placenta. Trophoblast Research. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1936-9_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-1936-9_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1938-3

  • Online ISBN: 978-1-4757-1936-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation