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Free hCGβ and Nongonadal Neoplasms

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Glycoprotein Hormones

Part of the book series: Serono Symposia USA ((SERONOSYMP))

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Abstract

The production of human chorionic gonadotropin (hCG) and its free alpha subunit (hCGα) and beta subunit (hCGβ) by nongonadal neoplasms is controversial. Following the initial report (1), numerous studies have provided indirect evidence for the production of hCG, hCG-like substances, or free subunits by nongonadal cancers (2–8). Indeed, between 1973 and 1985, 105 studies reported immunoreactive hCG in sera of nontrophoblastic tumor patients; between 1962 and 1986, 107 investigations showed the immunocytochemical localization of hCG in various tissue (9, 10). However, these results were questionable, since most investigations used polyclonal and monoclonal antibodies lacking the required specificity. One of the major problems was that most antibodies cross-reacted with human luteinizing hormone (hLH) (6, 11, 12). More recently developed assays based on monoclonal antibodies continued to display low, but significant, cross-reactivity with hLH (13–17). More importantly, most assays were unable to distinguish between the intact hCG molecule and the free hCGβ-subunit. Indeed, the observed cross-reactivity of intact hCG varied between 3% and 100% in radioimmunoassays used for the detection of free hCGβ. It was much lower, but still significant (0.2% to 4%), with most immunoradiometric assays (m-IRMAs) for free hCGβ based on monoclonal antibodies (13–15, 18–20). Finally, the nomenclature for hCGβ assays is ambiguous, since the same designation was given to at least two types of assays with widely different specificities, including those measuring only the free hCGβ-subunit and those measuring both intact hCG and the free hCGβ-subunit (21, 22). Similarly, the nomenclature for hCG assays may be misinterpreted, since these assays also measure the free hCGβ-subunit in addition to hCG (23).

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References

  1. Reeves RL, Tesluk H, Harrison CE. Precocious puberty associated with hepatoma. J Clin Endocrinol Metab 1959; 19: 1651–60.

    Article  PubMed  CAS  Google Scholar 

  2. Borkowski A, Muquardt C. Human chorionic gonadotropin in the plasma of normal nonpregnant subjects. N Engl J Med 1979; 301: 298–302.

    Article  PubMed  CAS  Google Scholar 

  3. Kahn CR, Rosen SW, Weintraub BD, Fajans SS, Gorden P. Ectopic production of chorionic gonadotropin and its subunits by islet-cell tumors. N Engl J Med 1977; 297: 565–9.

    Article  PubMed  CAS  Google Scholar 

  4. Rosen SW, Weintraub BD. Ectopic production of the isolated alpha subunit of the glycoprotein hormones. N Engl J Med 1974; 290: 1441–7.

    Article  PubMed  CAS  Google Scholar 

  5. Weintraub BD, Rosen WS. Ectopic production of the isolated beta subunit of human chorionic gonadotropin. J Clin Invest 1973; 52: 3135–42.

    Article  PubMed  CAS  Google Scholar 

  6. Tormey DC, Waalkes TP, Simon RM. Biological markers in breast carcinoma. Cancer 1977; 39: 2391–6.

    Article  PubMed  CAS  Google Scholar 

  7. Gailani S, Chu TM, Nussbaum A, Ostrander M, Christoff N. Human chorionic gonadotrophins (hCG) in nontrophoblastic neoplasms. Cancer 1976; 38: 1684–6.

    Article  PubMed  CAS  Google Scholar 

  8. Blackman MR, Weintraub BD, Rosen SW, Kourides IA, Steinwascher K, Gail MH. Human placental and pituitary glycoprotein hormones and their subunits as tumor markers: a quantitative assessment. J Natl Cancer Inst 1980; 65: 81–93.

    PubMed  CAS  Google Scholar 

  9. Hussa RO. Clinical applications of hCG tests: tumors. In: Hussa RO, ed. The clinical marker hCG. New York: Praeger, 1987: 119–36.

    Google Scholar 

  10. Hussa RO. Subunits of hCG. In: Hussa RO, ed. The clinical marker hCG. New York: Praeger, 1987: 161–78.

    Google Scholar 

  11. Papapetrou PD, Sakarelou NP, Braouzi H, Fessas PH. Ectopic production of human chorionic gonadotropin (hCG) by neoplasms: the value of measurements of immunoreactive hCG in the urine as a screening procedure. Cancer 1980; 45: 2583–92.

    Article  PubMed  CAS  Google Scholar 

  12. Monteiro JCMP, Ferguson KM, McKinna JA, Greening WP, Neville AM. Ectopic production of human chorionic gonadotrophin-like material by breast cancer. Cancer 1984; 53: 957–62.

    Article  PubMed  CAS  Google Scholar 

  13. Saller B, Clara R, Spöttl G, Siddle K, Mann K. Testicular cancer secretes intact human choriogonadotropin (hCG) and its free ß subunit: evidence that hCG (+hCG-β) assays are the most reliable in diagnosis and follow-up. Clin Chem 1990; 36: 234–9.

    PubMed  CAS  Google Scholar 

  14. Hay D, Murphy JR. Evaluating human choriogonadotropin heterogeneity in nongestational malignancy with monoclonal immunoassays. Oncology 1987; 44: 174–9.

    Article  PubMed  CAS  Google Scholar 

  15. Hay DL. Histological origins of discordant chorionic gonadotropin secretion in malignancy. J Clin Endocrinol Metab 1988; 66: 557–64.

    Article  PubMed  CAS  Google Scholar 

  16. Alfthan H, Haglund C, Dabek J, Ulf-Häkan S. Concentrations of human choriogonadotropin, its β-subunit, and the core fragment of the 13-subunit in serum and urine of men and nonpregnant women. Clin Chem 1992; 38: 1981–7.

    PubMed  CAS  Google Scholar 

  17. Alfthan H, Haglund C, Roberts P, Ulf-Häkan S. Elevation of free ß subunit of human choriogonadotropin and core ß fragment of human choriogonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease. Cancer Res 1992: 4628–33.

    Google Scholar 

  18. Hussa RO. Tissue localization of hCG. In: Hussa RO, ed. The clinical marker hCG. New York: Praeger, 1987; 52: 151–60.

    Google Scholar 

  19. Fan C, Goto S, Furuhashi Y, Tomoda Y. Radioimmunoassay of the serum free 13-subunit of human chorionic gonadotropin in trophoblastic disease. J Clin Endocrinol Metab 1987; 64: 313–8.

    Article  PubMed  CAS  Google Scholar 

  20. Mann K, Siddle K. Evidence for free beta-subunit secretion in so-called human chorionic gonadotropin-positive seminoma. Cancer 1988; 62: 2378–82.

    Article  PubMed  CAS  Google Scholar 

  21. Case records of the Massachusetts General Hospital (case 34–1983). N Engl J Med 1983; 309: 477–87.

    Article  Google Scholar 

  22. Lindstedt G, Lundberg PA, Hedman LA. Circulating choriogonadotropin ß subunit in a patient with primary amenorrhea and embryonal ovarian carcinoma. Clin Chim Acta 1980; 104: 195–200.

    Article  PubMed  CAS  Google Scholar 

  23. Cole LA, Kardana A. Discordant results in human chorionic gonadotropin assays. Clin Chem 1992; 38: 263–70.

    PubMed  CAS  Google Scholar 

  24. Ozturk M, Bellet D, Manil L, Hennen G, Frydman R, Wands JR. Physiological studies of human chorionic gonadotropin (hCG), ahCG, and ßhCG as measured by specific monoclonal immunoradiometric assays. Endocrinology 1987; 120: 549–58.

    Article  PubMed  CAS  Google Scholar 

  25. Griffin J, Odell WD. Ultrasensitive immunoradiometric assay for chorionic gonadotropin which does not cross-react with luteinizing hormone nor free ß chain of hCG and which detects hCG in blood of non-pregnant humans. J Immunol Methods 1987; 103: 275–83.

    Article  PubMed  CAS  Google Scholar 

  26. Odell WD, Griffin J. Pulsatile secretion of human chorionic gonadotropin in normal adults. N Engl J Med 1987; 317: 1688–91.

    Article  PubMed  CAS  Google Scholar 

  27. Ozturk M, Berkowitz R, Goldstein D, Bellet D, Wands JR. Differential production of human chorionic gonadotropin and free subunits in gestational trophoblastic disease. Am J Obstet Gynecol 1988; 158: 193–8.

    PubMed  CAS  Google Scholar 

  28. Stenman U-H, Alfthan H, Myllynen L, Seppälä M. Ultrarapid and highly sensitive time-resolved fluoroimmunometric assay for chorionic gonadotropin. Lancet 1983; 2: 647–9.

    Article  PubMed  CAS  Google Scholar 

  29. Bellet DH, Ozturk M, Bidart JM, Bohuon CJ, Wands JR. Sensitive and specific assay for human chorionic gonadotropin (hCG) based on anti-peptide and anti-hCG antibodies: construction and clinical implications. J Clin Endocrinol Metab 1986; 63: 1319–27.

    Article  PubMed  CAS  Google Scholar 

  30. Odell WD, Griffin J, Bashey HM, Snyder PJ. Secretion of chorionic gonadotropin by cultured human pituitary cells. J Clin Endocrinol Metab 1990; 71: 1318–21.

    Article  PubMed  CAS  Google Scholar 

  31. Hammond E, Griffin J, Odell WD. A chorionic gonadotropin-secreting human pituitary cell. J Clin Endocrinol Metab 1991; 72: 747–4.

    Article  PubMed  CAS  Google Scholar 

  32. Marcillac I, Troalen F, Bidart J-M, et al. Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms. Cancer Res 1992; 52: 3901–7.

    PubMed  CAS  Google Scholar 

  33. Madersbacher S, Klieber R, Mann K, et al. Free a-subunit, free 0-subunit of human chorionic gonadotropin (hCG), and intact hCG in sera of healthy individuals and testicular cancer patients. Clin Chem 1992; 38: 370–6.

    PubMed  CAS  Google Scholar 

  34. Braunstein GD, Vaaitukaitis JL, Carbone PP, Ross GT. Ectopic production of human chorionic gonadotrophin by neoplasms. Ann Med 1973; 78: 39–45.

    CAS  Google Scholar 

  35. Dexeus F, Logothetis C, Hossan E, Samuel ML. Carcinoembryonic antigen and beta-human chorionic gonadotropin as serum markers for advanced urothelial malignancies. J Urol 1986; 136: 403–7.

    PubMed  CAS  Google Scholar 

  36. Gropp C, Havemann K, Scheuer A. Ectopic hormones in lung cancer patients at diagnosis and during therapy. Cancer 1980; 46: 347–54.

    Article  PubMed  CAS  Google Scholar 

  37. Oberg K, Wide L. hCG and hCG subunits as tumour markers in patients with endocrine pancreatic tumours and carcinoids. Acta Endocrinol 1981; 98: 256–60.

    PubMed  CAS  Google Scholar 

  38. Rutanen E-M, Seppälä M. The hCG-f3 subunit radioimmunoassay in nontrophoblastic gynecological tumors. Cancer 1978; 41: 692–6.

    Article  PubMed  CAS  Google Scholar 

  39. Carenza L, di Gregorio R, Mocci C, Moro M, Pala A. Ectopic human chorionic gonadotropin: gynecological tumors and nonmalignant conditions. Gynecol Oncol 1980; 10: 32–9.

    Article  PubMed  CAS  Google Scholar 

  40. Hoermann R, Spoettl G, Moncayo R, Mann K. Evidence for the presence of human chorionic gonadotropin (hCG) and free 0-subunit of hCG in the human pituitary. J Clin Endocrinol Metab 1990; 71: 179–86.

    Article  PubMed  CAS  Google Scholar 

  41. Heitz PU, von Herbay G, Klöppel G. The expression of subunits of human chorionic gonadotropin (hCG) by nontrophoblastic, nonendocrine, and endocrine tumors. Am J Clin Pathol 1987; 88: 467–72.

    PubMed  CAS  Google Scholar 

  42. Papapetrou PD, Nicopoulou SCh. The origin of a human chorionic gonadotropin 13-subunit-core fragment excreted in the urine of patients with cancer. Acta Endocrinol 1986; 112: 415–22.

    PubMed  CAS  Google Scholar 

  43. Nagelberg SB, Marmorstein B, Khazaeli MB, Rosen SW. Isolated ectopic production of the free beta subunit of chorionic gonadotropin by an epidermoid carcinoma of unknown primary site. Cancer 1985; 55: 1924–30.

    Article  PubMed  CAS  Google Scholar 

  44. Wehmann RE, Nisula BC. Metabolic and renal clearance rates of purified human chorionic gonadotropin. J Clin Invest 1981; 68: 184–94.

    Article  PubMed  CAS  Google Scholar 

  45. Wehmann RE, Nisula BC. Renal clearance rates of the subunits of human chorionic gonadotropin in man. J Clin Endocrinol Metab 1980; 50: 674–9.

    Article  PubMed  CAS  Google Scholar 

  46. Djewitzki WSt. Uber einen fall von chorionepithelioma der harnblase. Virchows Arch Anat Physiol Klin Med 1904; 178: 451–64.

    Article  Google Scholar 

  47. Pick L. Uber die chorionepitheliomätnlich metastasierende form des magencarcinoms. Klin Wochenschr 1926; 5: 1728–9.

    Google Scholar 

  48. Vahlensieck W, Riede U, Wimmer B, Ihling C. Beta-human chorionic gonadotropin-positive extragonadal germ cell neoplasia of the renal pelvis. Cancer 1991; 67: 3146–9.

    Article  PubMed  Google Scholar 

  49. Park CH, Reid JD. Adenocarcinoma of the colon with choriocarcinoma in its metastases. Cancer 1980; 46: 570–5.

    Article  PubMed  CAS  Google Scholar 

  50. Obe JA, Rosen N, Koss LG. Primary choriocarcinoma of the urinary bladder. Cancer 1983; 52: 1405–9.

    Article  PubMed  CAS  Google Scholar 

  51. Kubosawa H, Nagao K, Kondo Y, Ishige H, Inaba N. Coexistence of adenocarcinoma and choriocarcinoma in the sigmoid colon. Cancer 1984; 54: 866–8.

    Article  PubMed  CAS  Google Scholar 

  52. Campo E, Algaba F, Palacin A, Germa R, Sole-Balcells FJ, Cardesa A. Placental proteins in high-grade urothelial neoplasms. An immunohistochemical study of human chorionic gonadotropin, human placental lactogen, and pregnancy-specific beta-l-glycoprotein. Cancer 1989; 63: 2497–504.

    Article  PubMed  CAS  Google Scholar 

  53. Hay DL. Discordant and variable production of human chorionic gonadotropin and its free a-and 0-subunits in early pregnancy. J Clin Endocrinol Metab 1985; 61: 1195–200.

    Article  PubMed  CAS  Google Scholar 

  54. Iles RK, Jenkins BJ, Oliver RTD, Blandy JP, Chard T. Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer. Br J Urol 1989; 64: 241–4.

    Article  PubMed  CAS  Google Scholar 

  55. Iles RK, Chard T. Human chorionic gonadotropin expression by bladder cancers: biology and clinical potential. J Urol 1991; 145; 453–8.

    PubMed  CAS  Google Scholar 

  56. McLoughlin J, Pepera T, Bridger J, Williams G. Serum and urinary levels of beta human chorionic gonadotrophin in patients with transitional cell carcinoma. Br J Cancer 1991; 63: 822–4.

    Article  PubMed  CAS  Google Scholar 

  57. Fetissof F, Bellet D, Guilloteau D, Maillot O. Hormone gonadotrophine chorionique et carcinome à cellules transitionnelles de la vessie. Ann Pathol 1988; 8: 276–80.

    PubMed  CAS  Google Scholar 

  58. Iles R. β-hCG expression by bladder cancers. Br J Cancer 1992; 65: 305.

    Article  PubMed  CAS  Google Scholar 

  59. Iles RK, Oliver RTD, Kitau M, Walker C, Chard T. In vitro secretion of human chorionic gonadotropin by bladder tumour cells. Br J Cancer 1987; 55: 623–6.

    Article  PubMed  CAS  Google Scholar 

  60. Iles RK, Purkis PE, Whitehead PC, Oliver RTD, Leigh I, Chard T. Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine “normal” and malignant epithelial cells. Br J Cancer 1990; 61: 663–6.

    Article  PubMed  CAS  Google Scholar 

  61. Young RH, Eble JN. Unusual forms of carcinoma of the urinary bladder. Hum Pathol 1991; 22: 948–65.

    Article  PubMed  CAS  Google Scholar 

  62. Martin JE, Jenkins BJ, Zuk RJ, et al. Human chorionic gonadotropin expression and histological findings as predictors of response to radiotherapy in carinoma of the bladder. Virchows Arch [A] 1989; 414: 273–7.

    Article  CAS  Google Scholar 

  63. Oliver RTD, Stephenson C, Collino CE, et al. Clinicopathological significance of immunoreactive beta-hCG production by bladder cancer. Mol Biother 1988; 1: 43–5.

    PubMed  CAS  Google Scholar 

  64. Burry AF, Munn SR, Arnold EP, et al. Trophoblastic metaplasia in urothelial carcinoma of the bladder. Br J Urol 1986; 58: 143–6.

    Article  PubMed  CAS  Google Scholar 

  65. Herr WH, Laudone VP, Badalament RA, et al. Bacillus Calmette-Guérin therapy alters the progression of superficial bladder cancer. J Clin Oncol 1988; 6: 1450–5.

    PubMed  CAS  Google Scholar 

  66. Lamm DL, Blumenstein BA, Crawford ED, Montie JE, Scardino P, Grossman HB, et al. A randomized trial of intravesical doxorubicin and immunotherapy with Bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med 1991; 325: 1205–9.

    Article  PubMed  CAS  Google Scholar 

  67. Cookson MS, Sarosdy MF. Management of stage T1 superficial bladder cancer with intravesical Bacillus Calmette-Guérin therapy. J Urol 1992; 148: 797–801.

    PubMed  CAS  Google Scholar 

  68. Brosmann SA. Experience with Bacillus Calmette-Guérin in patients with superficial bladder cancer. J Urol 1982; 128: 27–30.

    Google Scholar 

  69. Ratlif TL, Gillen DP, Catalona WJ. Requirement of a thymus dependent immune response for BCG-mediated antitumor activity. J Urol 1987; 137: 155–8.

    Google Scholar 

  70. Becich MJ, Carroll S, Ratliff TL. Internalization of Bacille Calmette-Guérin. J Urol 1991; 145: 1316–24.

    PubMed  CAS  Google Scholar 

  71. Cornel EB, Van Moorselaar JA, Van Stratum P, Debruyne MJ, Schalken JA. Antitumor effects of Bacillus Calmette-Guérin in a syngeneic rat bladder tumor model system RT323. J Urol 1993; 149: 179–82.

    PubMed  CAS  Google Scholar 

  72. Prescott S, James K, Hargreave TB, Chisholm GD, Smyth JF. Intravesical Evans strain BCG therapy: quantitative immunohistochemical analysis of the immune response within the bladder wall. J Urol 1992; 147: 16536–42.

    Google Scholar 

  73. Böhle A, Nowc CH, Ulmer AJ, et al. Elevations of cytokines interleukin-1, interleukin-2 and tumor necrosis factor in the urine of patients after intravesical Bacillus Calmette-Guérin immunotherapy. J Urol 1990; 144: 59–63.

    PubMed  Google Scholar 

  74. Kuroda K, Brown EJ, Telle WB, Russel DG, Ratliff TL. Characterization of the internalization of Bacillus Calmette-Guérin by human bladder tumor cells. J Clin Invest 1993; 91: 69–76.

    Article  PubMed  CAS  Google Scholar 

  75. Rouas N, Christophe S, Bellet D, Troalen F, Guillet JG, Bidart J-M Immune recognition of a molecule naturally presented as a monomeric or an oligo-meric structure: the model of the human chorionic gonadotropin a subunit. Mol Immunol 1992; 29: 883–93.

    Article  PubMed  CAS  Google Scholar 

  76. Rouas N, Christophe S, Housseau F, Bellet D, Guillet JG, Bidart J-M. Influence of protein quaternary structure on antigen processing. J Immunol 1993; 150: 782–92.

    PubMed  CAS  Google Scholar 

  77. Gedde-Dahl T III, Spurkland A, Eriksen JA, Thorsby E, Gaudernack G. Memory T cells of a patient with follicular thyroid carcinoma recognize peptides derived from mutated p21 ras (Gln-Leu 61). Int Immunol 1992; 11: 1331–7.

    Article  Google Scholar 

  78. Richardson RL, Schoumacher RA, Fer MF. The unrecognized extragonadal germ cell cancer syndrome. Ann Intern Med 1981; 94: 181–6.

    PubMed  CAS  Google Scholar 

  79. Greco A, Vaughn WK, Hainsworth JD. Advanced poorly differentiated carcinoma of unknown primary site: recognition of a treatable syndrome. Ann Intern Med 1986; 104: 547–53.

    PubMed  CAS  Google Scholar 

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Bellet, D. et al. (1994). Free hCGβ and Nongonadal Neoplasms. In: Lustbader, J.W., Puett, D., Ruddon, R.W. (eds) Glycoprotein Hormones. Serono Symposia USA. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-8386-4_20

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