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. 1989 Jul-Aug;62(4):367–378.

Urinary gonadotropin fragment (UGF) measurements in the diagnosis and management of ovarian cancer.

L A Cole 1, J H Nam 1
PMCID: PMC2589077  PMID: 2596125

Abstract

UGF is a small peptide present in the urines and tissues of patients with gynecologic cancers. Published research (which, at present, mainly comes from our laboratory) on the general application of UGF as a tumor marker, and on its use in the diagnosis of ovarian cancer, is reviewed, and new studies on its use, alone and with CA125, in the management of patients with ovarian cancer, are presented. In 234 healthy women, 89 with benign disease, and 79 with ovarian cancer, UGF levels were above 3 fmol/ml (low cut-off) in 12 percent, 7 percent, and 82 percent, respectively, and above 8 fmol/ml (high cut-off) in 1.7 percent, less than 1.1 percent, and 59 percent, respectively. Similarly, 11 percent, 14 percent, and 70 percent, respectively, had CA125 levels above 35 U/ml (low cut-off), and less than 1.9 percent, 1.2 percent, and 49 percent had levels above a 200 U/ml (high cut-off). Ideally, the higher UGF and CA125 cut-offs should be used for diagnostic applications, like differentiation of a benign from a malignant pelvic mass (false-positive rate: UGF, less than 1.1 percent; CA125, 1.2 percent), but raising the cut-offs diminishes sensitivities for malignancy (UGF, 59 percent; CA125, 49 percent). The populations detected by the two markers only partially overlap, however, so that, together, UGF or CA125 can identify 75 percent of malignant pelvic masses. Levels of UGF (cut-off, greater than 3 fmol/ml) and CA125 (35 U/ml) were also monitored in 30 women undergoing therapy for ovarian cancer. Clinical observations were reflected at each clinic visit by UGF alone in 67 percent, by CA125 alone in 57 percent, and by UGF and CA125 together in 87 percent of cases. While separately UGF and CA125 levels predicted 71 percent and 57 percent, together they forecast 86 percent of recurrent cancers prior to clinical manifestations. UGF and CA125 should be used together in the detection and management of ovarian cancers.

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Selected References

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  1. Akar A. H., Wehmann R. E., Blithe D. L., Blacker C., Nisula B. C. A radioimmunoassay for the core fragment of the human chorionic gonadotropin beta-subunit. J Clin Endocrinol Metab. 1988 Mar;66(3):538–545. doi: 10.1210/jcem-66-3-538. [DOI] [PubMed] [Google Scholar]
  2. Alvarez R. D., To A., Boots L. R., Shingleton H. M., Hatch K. D., Hubbard J., Soong S. J., Potter M. E. CA125 as a serum marker for poor prognosis in ovarian malignancies. Gynecol Oncol. 1987 Mar;26(3):284–289. doi: 10.1016/0090-8258(87)90019-9. [DOI] [PubMed] [Google Scholar]
  3. Atack D. B., Nisker J. A., Allen H. H., Tustanoff E. R., Levin L. CA 125 surveillance and second-look laparotomy in ovarian carcinoma. Am J Obstet Gynecol. 1986 Feb;154(2):287–289. doi: 10.1016/0002-9378(86)90657-5. [DOI] [PubMed] [Google Scholar]
  4. Bast R. C., Jr, Klug T. L., St John E., Jenison E., Niloff J. M., Lazarus H., Berkowitz R. S., Leavitt T., Griffiths C. T., Parker L. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med. 1983 Oct 13;309(15):883–887. doi: 10.1056/NEJM198310133091503. [DOI] [PubMed] [Google Scholar]
  5. Birken S., Armstrong E. G., Kolks M. A., Cole L. A., Agosto G. M., Krichevsky A., Vaitukaitis J. L., Canfield R. E. Structure of the human chorionic gonadotropin beta-subunit fragment from pregnancy urine. Endocrinology. 1988 Jul;123(1):572–583. doi: 10.1210/endo-123-1-572. [DOI] [PubMed] [Google Scholar]
  6. Blithe D. L., Akar A. H., Wehmann R. E., Nisula B. C. Purification of beta-core fragment from pregnancy urine and demonstration that its carbohydrate moieties differ from those of native human chorionic gonadotropin-beta. Endocrinology. 1988 Jan;122(1):173–180. doi: 10.1210/endo-122-1-173. [DOI] [PubMed] [Google Scholar]
  7. Canney P. A., Moore M., Wilkinson P. M., James R. D. Ovarian cancer antigen CA125: a prospective clinical assessment of its role as a tumour marker. Br J Cancer. 1984 Dec;50(6):765–769. doi: 10.1038/bjc.1984.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen D. X., Schwartz P. E., Li X. G., Yang Z. Evaluation of CA 125 levels in differentiating malignant from benign tumors in patients with pelvic masses. Obstet Gynecol. 1988 Jul;72(1):23–27. [PubMed] [Google Scholar]
  9. Cole L. A., Birken S. Origin and occurrence of human chorionic gonadotropin beta-subunit core fragment. Mol Endocrinol. 1988 Sep;2(9):825–830. doi: 10.1210/mend-2-9-825. [DOI] [PubMed] [Google Scholar]
  10. Cole L. A., Hartle R. J., Laferla J. J., Ruddon R. W. Detection of the free beta subunit of human chorionic gonadotropin (HCG) in cultures of normal and malignant trophoblast cells, pregnancy sera, and sera of patients with choriocarcinoma. Endocrinology. 1983 Sep;113(3):1176–1178. doi: 10.1210/endo-113-3-1176. [DOI] [PubMed] [Google Scholar]
  11. Cole L. A., Hussa R. O., Rao C. V. Discordant synthesis and secretion of human chorionic gonadotropin and subunits by cervical carcinoma cells. Cancer Res. 1981 May;41(5):1615–1619. [PubMed] [Google Scholar]
  12. Cole L. A., Kroll T. G., Ruddon R. W., Hussa R. O. Differential occurrence of free beta and free alpha subunits of human chorionic gonadotropin (hCG) in pregnancy sera. J Clin Endocrinol Metab. 1984 Jun;58(6):1200–1202. doi: 10.1210/jcem-58-6-1200. [DOI] [PubMed] [Google Scholar]
  13. Cole L. A., Restrepo-Candelo H., Lavy G., Decherney A. hCG free beta-subunit an early marker of outcome of in vitro fertilization clinical pregnancies. J Clin Endocrinol Metab. 1987 Jun;64(6):1328–1330. doi: 10.1210/jcem-64-6-1328. [DOI] [PubMed] [Google Scholar]
  14. Cole L. A., Schwartz P. E., Wang Y. X. Urinary gonadotropin fragments (UGF) in cancers of the female reproductive system. I. Sensitivity and specificity, comparison with other markers. Gynecol Oncol. 1988 Sep;31(1):82–90. doi: 10.1016/0090-8258(88)90273-9. [DOI] [PubMed] [Google Scholar]
  15. Cole L. A., Wang Y. X., Elliott M., Latif M., Chambers J. T., Chambers S. K., Schwartz P. E. Urinary human chorionic gonadotropin free beta-subunit and beta-core fragment: a new marker of gynecological cancers. Cancer Res. 1988 Mar 1;48(5):1356–1360. [PubMed] [Google Scholar]
  16. Elegbe R. A., Pattillo R. A., Hussa R. O., Hoffmann R. G., Damole I. O., Finlayson W. E. Alpha subunit and human chorionic gonadotropin in normal pregnancy and gestational trophoblastic disease. Obstet Gynecol. 1984 Mar;63(3):335–337. [PubMed] [Google Scholar]
  17. Finkler N. J., Benacerraf B., Lavin P. T., Wojciechowski C., Knapp R. C. Comparison of serum CA 125, clinical impression, and ultrasound in the preoperative evaluation of ovarian masses. Obstet Gynecol. 1988 Oct;72(4):659–664. [PubMed] [Google Scholar]
  18. Fukazawa I., Inaba N., Ota Y., Sato N., Shirotake S., Iwasawa H., Sato T., Takamizawa H., Wiklund B. Serum levels of six tumor markers in patients with benign and malignant gynecological disease. Arch Gynecol Obstet. 1988;243(2):61–68. doi: 10.1007/BF00932971. [DOI] [PubMed] [Google Scholar]
  19. Good A., Ramos-Uribe M., Ryan R. J., Kempers R. D. Molecular forms of human chorionic gonadotropin in serum, urine, and placental extracts. Fertil Steril. 1977 Aug;28(8):846–850. [PubMed] [Google Scholar]
  20. Hay D. L. Discordant and variable production of human chorionic gonadotropin and its free alpha- and beta-subunits in early pregnancy. J Clin Endocrinol Metab. 1985 Dec;61(6):1195–1200. doi: 10.1210/jcem-61-6-1195. [DOI] [PubMed] [Google Scholar]
  21. Kahn C. R., Rosen S. W., Weintraub B. D., Fajans S. S., Gorden P. Ectopic production of chorionic gonadotropin and its subunits by islet-cell tumors. A specific marker for malignancy. N Engl J Med. 1977 Sep 15;297(11):565–569. doi: 10.1056/NEJM197709152971101. [DOI] [PubMed] [Google Scholar]
  22. Kardana A., Taylor M. E., Rowan A. J., Read D. A., Bagshawe K. D. Characterisation of antibodies to urinary gonadotrophin peptide. J Immunol Methods. 1989 Mar 10;118(1):53–58. doi: 10.1016/0022-1759(89)90052-5. [DOI] [PubMed] [Google Scholar]
  23. Kardana A., Taylor M. E., Southall P. J., Boxer G. M., Rowan A. J., Bagshawe K. D. Urinary gonadotrophin peptide--isolation and purification, and its immunohistochemical distribution in normal and neoplastic tissues. Br J Cancer. 1988 Sep;58(3):281–286. doi: 10.1038/bjc.1988.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kato Y., Braunstein G. D. Beta-core fragment is a major form of immunoreactive urinary chorionic gonadotropin in human pregnancy. J Clin Endocrinol Metab. 1988 Jun;66(6):1197–1201. doi: 10.1210/jcem-66-6-1197. [DOI] [PubMed] [Google Scholar]
  25. Khazaeli M. B., Hedayat M. M., Hatch K. D., To A. C., Soong S. J., Shingleton H. M., Boots L. R., LoBuglio A. F. Radioimmunoassay of free beta-subunit of human chorionic gonadotropin as a prognostic test for persistent trophoblastic disease in molar pregnancy. Am J Obstet Gynecol. 1986 Aug;155(2):320–324. doi: 10.1016/0002-9378(86)90818-5. [DOI] [PubMed] [Google Scholar]
  26. Klug T. L., Bast R. C., Jr, Niloff J. M., Knapp R. C., Zurawski V. R., Jr Monoclonal antibody immunoradiometric assay for an antigenic determinant (CA 125) associated with human epithelial ovarian carcinomas. Cancer Res. 1984 Mar;44(3):1048–1053. [PubMed] [Google Scholar]
  27. Krebs H. B., Goplerud D. R., Kilpatrick S. J., Myers M. B., Hunt A. Role of Ca 125 as tumor marker in ovarian carcinoma. Obstet Gynecol. 1986 Apr;67(4):473–477. [PubMed] [Google Scholar]
  28. Krichevsky A., Armstrong E. G., Schlatterer J., Birken S., O'Connor J., Bikel K., Silverberg S., Lustbader J. W., Canfield R. E. Preparation and characterization of antibodies to the urinary fragment of the human chorionic gonadotropin beta-subunit. Endocrinology. 1988 Jul;123(1):584–593. doi: 10.1210/endo-123-1-584. [DOI] [PubMed] [Google Scholar]
  29. Malkasian G. D., Jr, Knapp R. C., Lavin P. T., Zurawski V. R., Jr, Podratz K. C., Stanhope C. R., Mortel R., Berek J. S., Bast R. C., Jr, Ritts R. E. Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease. Am J Obstet Gynecol. 1988 Aug;159(2):341–346. doi: 10.1016/s0002-9378(88)80081-4. [DOI] [PubMed] [Google Scholar]
  30. Masure H. R., Jaffee W. L., Sickel M. A., Birken S., Canfield R. E., Vaitukaitis J. L. Characterization of a small molecular size urinary immunoreactive human chorionic gonadotropin (hCG)-like substance produced by normal placenta and by hCG-secreting neoplasms. J Clin Endocrinol Metab. 1981 Nov;53(5):1014–1020. doi: 10.1210/jcem-53-5-1014. [DOI] [PubMed] [Google Scholar]
  31. Meire H. B., Farrant P., Guha T. Distinction of benign from malignant ovarian cysts by ultrasound. Br J Obstet Gynaecol. 1978 Dec;85(12):893–899. doi: 10.1111/j.1471-0528.1978.tb15850.x. [DOI] [PubMed] [Google Scholar]
  32. Nagelberg S. B., Cole L. A., Rosen S. W. A novel form of ectopic human chorionic gonadotrophin beta-subunit in the serum of a woman with epidermoid cancer. J Endocrinol. 1985 Dec;107(3):403–408. doi: 10.1677/joe.0.1070403. [DOI] [PubMed] [Google Scholar]
  33. O'Connor J. F., Schlatterer J. P., Birken S., Krichevsky A., Armstrong E. G., McMahon D., Canfield R. E. Development of highly sensitive immunoassays to measure human chorionic gonadotropin, its beta-subunit, and beta core fragment in the urine: application to malignancies. Cancer Res. 1988 Mar 1;48(5):1361–1366. [PubMed] [Google Scholar]
  34. Odell W. D., Griffin J. Pulsatile secretion of human chorionic gonadotropin in normal adults. N Engl J Med. 1987 Dec 31;317(27):1688–1691. doi: 10.1056/NEJM198712313172702. [DOI] [PubMed] [Google Scholar]
  35. Ozturk M., Bellet D., Manil L., Hennen G., Frydman R., Wands J. Physiological studies of human chorionic gonadotropin (hCG), alpha hCG, and beta hCG as measured by specific monoclonal immunoradiometric assays. Endocrinology. 1987 Feb;120(2):549–558. doi: 10.1210/endo-120-2-549. [DOI] [PubMed] [Google Scholar]
  36. Papapetrou P. D., Nicopoulou S. C. The origin of a human chorionic gonadotropin beta-subunit-core fragment excreted in the urine of patients with cancer. Acta Endocrinol (Copenh) 1986 Jul;112(3):415–422. doi: 10.1530/acta.0.1120415. [DOI] [PubMed] [Google Scholar]
  37. Papapetrou P. D., Nicopoulou S. C. The origin of a human chorionic gonadotropin beta-subunit-core fragment excreted in the urine of patients with cancer. Acta Endocrinol (Copenh) 1986 Jul;112(3):415–422. doi: 10.1530/acta.0.1120415. [DOI] [PubMed] [Google Scholar]
  38. Requard C. K., Mettler F. A., Jr, Wicks J. D. Preoperative sonography of malignant ovarian neoplasms. AJR Am J Roentgenol. 1981 Jul;137(1):79–82. doi: 10.2214/ajr.137.1.79. [DOI] [PubMed] [Google Scholar]
  39. Schroeder H. R., Halter C. M. Specificity of human beta-choriogonadotropin assays for the hormone and for an immunoreactive fragment present in urine during normal pregnancy. Clin Chem. 1983 Apr;29(4):667–671. [PubMed] [Google Scholar]
  40. Schwartz P. E., Chambers S. K., Chambers J. T., Gutmann J., Katopodis N., Foemmel R. Circulating tumor markers in the monitoring of gynecologic malignancies. Cancer. 1987 Aug 1;60(3):353–361. doi: 10.1002/1097-0142(19870801)60:3<353::aid-cncr2820600312>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  41. Stenman U. H., Alfthan H., Ranta T., Vartiainen E., Jalkanen J., Seppälä M. Serum levels of human chorionic gonadotropin in nonpregnant women and men are modulated by gonadotropin-releasing hormone and sex steroids. J Clin Endocrinol Metab. 1987 Apr;64(4):730–736. doi: 10.1210/jcem-64-4-730. [DOI] [PubMed] [Google Scholar]
  42. Vaitukaitis J. L. Changing placental concentrations of human chorionic gonadotropin and its subunits during gestation. J Clin Endocrinol Metab. 1974 May;38(5):755–760. doi: 10.1210/jcem-38-5-755. [DOI] [PubMed] [Google Scholar]
  43. Vaitukaitis J. L. Immunologic and physical characterization of human chorionic gonadotropin (hCG) secreted by tumors. J Clin Endocrinol Metab. 1973 Oct;37(4):505–514. doi: 10.1210/jcem-37-4-505. [DOI] [PubMed] [Google Scholar]
  44. Vaitukaitis J. L. Immunologic and physical characterization of human chorionic gonadotropin (hCG) secreted by tumors. J Clin Endocrinol Metab. 1973 Oct;37(4):505–514. doi: 10.1210/jcem-37-4-505. [DOI] [PubMed] [Google Scholar]
  45. Vasilev S. A., Schlaerth J. B., Campeau J., Morrow C. P. Serum CA 125 levels in preoperative evaluation of pelvic masses. Obstet Gynecol. 1988 May;71(5):751–756. [PubMed] [Google Scholar]
  46. Wang Y. X., Schwartz P. E., Chambers J. T., Cole L. A. Urinary gonadotropin fragments (UGF) in cancers of the female reproductive system. II. Initial serial studies. Gynecol Oncol. 1988 Sep;31(1):91–102. doi: 10.1016/0090-8258(88)90274-0. [DOI] [PubMed] [Google Scholar]
  47. Wehmann R. E., Nisula B. C. Characterization of a discrete degradation product of the human chorionic gonadotropin beta-subunit in humans. J Clin Endocrinol Metab. 1980 Jul;51(1):101–105. doi: 10.1210/jcem-51-1-101. [DOI] [PubMed] [Google Scholar]
  48. Weintraub B. D., Rosen S. W. Ectopic production of the isolated beta subunit of human chorionic gonadotropin. J Clin Invest. 1973 Dec;52(12):3135–3142. doi: 10.1172/JCI107513. [DOI] [PMC free article] [PubMed] [Google Scholar]

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