The long-term objective is to establish the role of urinary hCG free beta-subunit and beta-fragment as clinical markers for the common gynecologic cancers. CLINICAL OBJECTIVES a) To determine the proportion of patients with gynecologic cancer having elevated urinary hCG free beta-subunit or beta- fragment titers. We propose examining titers in fluids from 80- 100 subjects/yr with newly diagnosed cancer. b) To examine the use of urinary free beta-subunit and beta- fragment as markers for progression of chemotherapy (1-4 regimens, 10-12 subjects/yr each) and radiotherapy (10-12 patients/yr). c) To evaluate the use of these markers in following cervical cancer by measuring titers in urines from patients with precancerous cervical changes (100/yr). Urines will also be collected from patients attending the general gynecology clinic (500-700/yr) to correlate free beta-subunit and beta-fragment titers with Pap smear screening to see if the former will function as an alternative or back-up assay to the Pap smear. OTHER OBJECTIVES a) To develop a single immunoassay for quantitating total urinary beta-subunit (hCG plus free beta-subunit and beta-fragment) for use in cancer detection. b) To investigate the origins of beta-fragment (the principal form of beta-subunit in urines). Molecules in cancer tissues (10-20 surgical specimens/yr) will be compared with beta-fragment in urine by immunoassays and gel filtration. PILOT STUDIES Parallel urines and sera were examined from 42 subjects with active gynecologic cancers, and hCG, free beta-subunit and beta- fragment (found only in urine) measured using immunoassays. Consistent with the serum studies of others, we found 19% of subjects positive for hCG or free beta-subunit. In urine, however, 73% of patients had elevated free beta-subunit or beta-fragment titers (includes 25% with hCG). Over 70% of patients with early disease (stage I or II) had elevated titers. Average titers of urinary beta-fragment were, on a molar basis, 7 -fold greater than those of serum hCG. In a control study of 16 healthy subjects, 1 had a low-positive urinary beta-fragment titer. The efficacy of free beta-subunit and beta-fragment as screeing markers for gynecologic malignancies and for determining response to therapy will be further evaluated.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA046828-01
Application #
3190258
Study Section
Pathology B Study Section (PTHB)
Project Start
1988-03-01
Project End
1991-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kardana, A; Cole, L A (1997) The stability of hCG and free beta-subunit in serum samples. Prenat Diagn 17:141-7
Isozaki, T; Palomaki, G E; Bahado-Singh, R O et al. (1997) Screening for Down syndrome pregnancy using beta-core fragment: prospective study. Prenat Diagn 17:407-13
Kardana, A; Braunstein, G D; Cole, L A (1996) Gonadotropin beta-subunit nicking enzyme (GBNE), a potential marker of early malignancies. Oncol Res 8:13-6
Cole, L A; Tanaka, A; Kim, G S et al. (1996) Beta-core fragment (beta-core/UGF/UGP), a tumor marker: a 7-year report. Gynecol Oncol 60:264-70
Tanaka, A; Cole, L A (1994) Improved methods for detecting beta-core in normal and cancer patient urines. Clin Chem 40:2317-8
Cole, L A; Kardana, A; Seifer, D B et al. (1994) Urine hCG beta-subunit core fragment, a sensitive test for ectopic pregnancy. J Clin Endocrinol Metab 78:497-9
Kardana, A; Cole, L A (1994) Human chorionic gonadotropin beta-subunit nicking enzymes in pregnancy and cancer patient serum. J Clin Endocrinol Metab 79:761-7
Cole, L A; Seifer, D B; Kardana, A et al. (1993) Selecting human chorionic gonadotropin immunoassays: consideration of cross-reacting molecules in first-trimester pregnancy serum and urine. Am J Obstet Gynecol 168:1580-6
Cole, L A; Kardana, A; Park, S Y et al. (1993) The deactivation of hCG by nicking and dissociation. J Clin Endocrinol Metab 76:704-10
Cole, L A; Kardana, A (1992) Discordant results in human chorionic gonadotropin assays. Clin Chem 38:263-70

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