Female sex steroid receptors in postmenopausal endometrial carcinoma and biochemical response to an antiestrogen.

Estradici and progesterone receptor concentrations were determined in cytoplasmic and nuclear fractions of endometrial cancer specimens taken from 43 postmenopausal women. In addition to receptors, ornithine decarboxylase and 17/?-estradiol hydroxysteroid dehydrogenase activities were also meas ured before and after antiestrogen treatment to evaluate hor mone sensitivity of the tumors. Fifteen patients received tamoxifen p.o. (40 mg daily for 5 to 7 days; Group 1) and 10 patients ingested 10 mg of tamoxifen 8 and 4 hr prior to a second endometrial sampling (Group 2). All tumors except one contained variable (often large) amounts of total estradiol receptors (mean, -1.8 pmol/mg DNA) in the range of those observed in the late proliferative phase of the cycle. The total progesterone receptor concentra tion (mean, ~1.5 pmol/mg DNA) was in the range of the late secretory phase and was considered undetectable or insignif icant (<0.3 pmol/mg DNA) in 10 cases. Although higher levels of receptors were observed in well-differentiated cancers, no significant correlation was found between receptor concentra tions and histological grading. Both receptors concentrated primarily in the cytoplasm. However, in 11 and 5 cases, re spectively, the majority of estradiol and progesterone receptors were located in the nuclei. Following tamoxifen administration, progesterone receptor concentrations in Group 1 increased significantly (p < 0.05), but ornithine decarboxylase activity did not. Because tamoxifen may have induced a rapid and transitory increase of enzyme activity, ornithine decarboxylase was studied in Group 2 pa tients. Again no change in the enzyme activity was observed. Progesterone receptor did not vary, but nuclear estradiol re ceptor increased, indicating the tamoxifen effectiveness. No meaningful changes occurred in 17/?-estradiol hydroxysteroid dehydrogenase activities in either group. Estrone, estradiol, and progesterone were also measured in serum. Mean estrone values [33.8 ±2.5 (S.E.) pg/ml] were greater than mean estradiol concentrations (23.6 ±5 pg/ml). Estrone values increased significantly (p < 0.01) from wellto less-differentiated tumors in relation to body weight, whereas progesterone (<1 ng/ml) and estradiol concentrations did not. All steroid concentrations were unchanged after tamoxifen. We conclude that (a) measurements of both cytoplasmic and nuclear receptors are necessary to accurately report receptor ' Present address: The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey. Pa. 17033. 2 On leave from Instituto de Oncologia "Angel H. Rotto," Buenos Aires. ' Supported by INSERM Contract 76-5-478 A. To whom requests for reprints should be addressed, at Lab Hormones, 94270 Bicetre, France. Received March 15, 1979; accepted December 11,1980. concentrations; (b) further trial with tamoxifen challenge test is justified to predict hormone responsiveness; and (c) this an tiestrogen may become an important component in the treat ment of advanced or metastatic endometrial carcinoma.