QUANTITATIVE-ANALYSES OF EPIDERMAL GROWTH-FACTOR RECEPTORS, HER-2 NEUONCOPROTEIN AND CATHEPSIN-D IN NONMALIGNANT AND MALIGNANT UTERI/

BACKGROUND. Hormone receptors and oncoproteins are receiving increased attention as possible prognostic factors in different carcinomas. Few data are available regarding quantification of their levels of expres sion in gynecologic malignancies. METHODS. Epidermal growth factor (EG F) receptor specific binding capacities and affinities were measured b y ligand binding assay using [I-125]EGF in a competition mode with Acc ufit(R) software (Lundon Software, Inc., Middlefield, OH). HER-2/neu o ncoprotein was extracted from membranes and measured using an enzyme-l inked immunosorbent assay. Cathepsin D was measured by an immunoradiom etric assay using cytosols for steroid receptor analyses. RESULTS. EGF receptors in 23 nonmalignant uteri ranged from undetectable to 50 fmo l/mg membrane protein (median, 0), with dissociation constant values o f 1.2 x 10(-9) M to 8.5 x 10(-10) M, compared with EGF receptors in 76 endometrial cancers that ranged from undetectable to 7674 fmol/mg (me dian, 52). HER-2/neu oncoprotein ranged from undetectable to 2.9 HER-2 /neu units (HNU) /mu g protein (median, 0.6) in 41 nonmalignant uteri and from undetectable to 5.8 HNU/mu g protein (median, 2.5) in endomet rial cancers (n = 53). Cathepsin D ranged from 5 to 32 pmol/mg cytosol protein (median, 11) in 42 nonmalignant uteri and 18 to 144 pmol/mg p rotein (median, 42) in 29 endometrial cancers. CONCLUSIONS, Determinat ion of the frequency and levels of EGF receptors, HER-2/neu protein, a nd cathepsin D in uteri with and without cancer and the availability o f reference materials developed in our laboratory will allow evaluatio n of their prognostic value in cancers of the uterus. (C) 1996 America n Cancer Society.