This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O'Connor, J. F. Articles by Canfield, R. E. Search for Related Content PubMed PubMed Citation Articles by O'Connor, J. F. Articles by Canfield, R. E.

Development of Highly Sensitive Immunoassays to Measure Human Chorionic Gonadotropin, Its ß-Subunit, and ß Core Fragment in the Urine: Application to Malignancies¹

Departments of Pathology [J. F. O., A. K., E. G. A.], and Medicine [J. P. S., S. B., A. K., D. M., R. E. C.], College of Physicians and Surgeons of Columbia University, New York, New York 10032

A variety of malignancies have been associated with the presence of human chorionic gonadotropin, hCG, its subunits, and fragments of its ß-subunit in blood and urine. The usefulness of these hCG-related tumor markers in nontrophoblastic malignancies has been inhibited by inadequate assay techniques. In order to achieve the required sensitivity and specificity, concentration steps and other procedures to remove cross-reacting human luteinizing hormone were necessary. In addition, the coexistence of a fragment of the hCG-ß or ß human luteinizing hormone subunit contributes to significant errors of measurement in urine. The importance of the hCG-ß fragment as a potential tumor marker has been recognized previously but no method was available to measure this antigen readily. We report here the development of a series of radioimmunometric, two-site assays which will accurately measure hCG, hCG-ß subunit, and the ß-subunit fragment directly in small volumes of unprocessed urine. These assays are highly specific, extremely sensitive, and not labor intensive since they employ microtiter plate procedures. Application of these assays to urine samples from patients with gynecological malignancies indicated that over 50% of all patients tested excreted the hCG-ß fragment in their urine. Also, this fragment comprised more than 50% of the moles of hCG immunoreactive components present in the specimens that were positive for hCG. This cancer marker is also demonstrable in trophoblastic malignant states such as choriocarcinoma in which the low molecular weight fragment can also be visualized directly by immunoblotting procedures. We conclude that a search for hCG immunoreactivity in the urine of patients with malignancies will be improved by the inclusion of accurte measurements of the prominent quantities of the ß fragment excreted by these individuals.

¹ Supported by NIH Grant P01HD-15454, NIEHS Contract NO-1-ES-4-5054, and NIH Grant RR00645.

² To whom requests for reprints should be addressed, at Columbia University College of Physicians and Surgeons, Clinical Research Center, PH 4-124, 630 West 168th Street, New York, NY 10032.

³ Present address: Hybritech Incorporated, 11085 Torreyana Road, P. O. Box 269006(92126), San Diego, CA 92121.

Received 5/20/87. Revised 11/19/87. Accepted 12/ 2/87.

This article has been cited by other articles:

				A. G. Ronnenberg, S. A. Venners, X. Xu, C. Chen, L. Wang, W. Guang, A. Huang, and X. Wang Preconception B-Vitamin and Homocysteine Status, Conception, and Early Pregnancy Loss Am. J. Epidemiol., August 1, 2007; 166(3): 304 - 312. [Abstract] [Full Text] [PDF]

				M. J. Perry, F. Ouyang, S. A. Korrick, S. A. Venners, C. Chen, X. Xu, B. L. Lasley, and X. Wang A Prospective Study of Serum DDT and Progesterone and Estrogen Levels across the Menstrual Cycle in Nulliparous Women of Reproductive Age Am. J. Epidemiol., December 1, 2006; 164(11): 1056 - 1064. [Abstract] [Full Text] [PDF]

				U.-H. Stenman, A. Tiitinen, H. Alfthan, and L. Valmu The classification, functions and clinical use of different isoforms of HCG Hum. Reprod. Update, November 1, 2006; 12(6): 769 - 784. [Abstract] [Full Text] [PDF]

				S. A. Venners, X. Liu, M. J. Perry, S. A. Korrick, Z. Li, F. Yang, J. Yang, B. L. Lasley, X. Xu, and X. Wang Urinary estrogen and progesterone metabolite concentrations in menstrual cycles of fertile women with non-conception, early pregnancy loss or clinical pregnancy Hum. Reprod., September 1, 2006; 21(9): 2272 - 2280. [Abstract] [Full Text] [PDF]

				S. A. Venners, S. Korrick, X. Xu, C. Chen, W. Guang, A. Huang, L. Altshul, M. Perry, L. Fu, and X. Wang Preconception Serum DDT and Pregnancy Loss: A Prospective Study Using a Biomarker of Pregnancy Am. J. Epidemiol., October 15, 2005; 162(8): 709 - 716. [Abstract] [Full Text] [PDF]

				R. McChesney, A. J. Wilcox, J. F. O'Connor, C. R. Weinberg, D. D. Baird, J. P. Schlatterer, D.R. McConnaughey, S. Birken, and R. E. Canfield Intact HCG, free HCG {beta} subunit and HCG {beta} core fragment: longitudinal patterns in urine during early pregnancy Hum. Reprod., April 1, 2005; 20(4): 928 - 935. [Abstract] [Full Text] [PDF]

				S. A. Venners, X. Wang, C. Chen, L. Wang, D. Chen, W. Guang, A. Huang, L. Ryan, J. O'Connor, B. Lasley, et al. Paternal Smoking and Pregnancy Loss: A Prospective Study Using a Biomarker of Pregnancy Am. J. Epidemiol., May 15, 2004; 159(10): 993 - 1001. [Abstract] [Full Text] [PDF]

				J. Chen, T. L. Thirkill, P. N. Lohstroh, S. R. Bielmeier, M. G. Narotsky, D. S. Best, R. A. Harrison, K. Natarajan, R. A. Pegram, J. W. Overstreet, et al. Bromodichloromethane Inhibits Human Placental Trophoblast Differentiation Toxicol. Sci., March 1, 2004; 78(1): 166 - 174. [Abstract] [Full Text] [PDF]

				J. Chen, G. C. Douglas, T. L. Thirkill, P. N. Lohstroh, S. R. Bielmeier, M. G. Narotsky, D. S. Best, R. A. Harrison, K. Natarajan, R. A. Pegram, et al. Effect of Bromodichloromethane on Chorionic Gonadotrophin Secretion by Human Placental Trophoblast Cultures Toxicol. Sci., November 1, 2003; 76(1): 75 - 82. [Abstract] [Full Text] [PDF]

				S.-I. Cho, M.B. Goldman, L.M. Ryan, C. Chen, A.I. Damokosh, D.C. Christiani, B.L. Lasley, J.F. O'Connor, A.J. Wilcox, and X. Xu Reliability of serial urine HCG as a biomarker to detect early pregnancy loss Hum. Reprod., April 1, 2002; 17(4): 1060 - 1066. [Abstract] [Full Text] [PDF]

				P. Mock, G. Kovalevskaya, J. F. O'Connor, and A. Campana Choriocarcinoma-like human chorionic gonadotrophin (HCG) and HCG bioactivity during the first trimester of pregnancy Hum. Reprod., October 1, 2000; 15(10): 2209 - 2214. [Abstract] [Full Text] [PDF]

				G. Kovalevskaya, S. Birken, T. Kakuma, J. Schlatterer, and J. F. O'Connor Evaluation of Nicked Human Chorionic Gonadotropin Content in Clinical Specimens by a Specific Immunometric Assay Clin. Chem., January 1, 1999; 45(1): 68 - 77. [Abstract] [Full Text] [PDF]

				U.-H. Stenman, L. Unkila-Kallio, J. Korhonen, and H. Alfthan Immunoprocedures for detecting human chorionic gonadotropin: clinical aspects and doping control Clin. Chem., July 1, 1997; 43(7): 1293 - 1298. [Abstract] [Full Text] [PDF]