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Estrogen (ER), progesterone (PR), and androgen receptors (AR) were determined by saturation analysis in 100 cases of primary ovarian cancer and correlated with patient survival. The mean follow-up period was 5.4 years (range, 4 to 6.5 years). Positivity for PR was associated with a significantly better survival rate (P less than 0.05). A similar observation was made for AR (P less than 0.05). Tumor ER content did not correlate with survival. Ten patients with tumors that had negative results for both PR and AR all died of the disease. In 91 cases of serous, endometrioid, and mucinous carcinomas, grade, stage, and tumor PR content, but not AR content, were identified as independent prognostic factors with the use of the Cox proportional hazards model. The relative risk of patients with PR-negative tumors was 2.3 times higher than that of patients with tumors containing high (greater than or equal to 30 fmol/mg) PR levels.

The histologic, morphometric, immunohistochemical, and ultrastructural study of a malignant Brenner tumor in a postmenopausal women presenting with vaginal bleeding is described. A comparison with transitional cell carcinomas is made, and the use of morphometry in grading the urotheliallike epithelium in malignant Brenner tumors is suggested. High preoperative urinary estrogen, low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and histologically confirmed atypical endometrial hyperplasia suggested a hyperestrogenism. The reduction in urinary estrogen and the increase in serum LH and FSH after tumor removal and the presence of aromatase activity detected in tumor microsomes confirmed that the tumor was synthesizing estrogen. Estrogen receptors were undetectable both by biochemical and histochemical analysis in the tumor.Cancer 58:754-760, 1986.

The results of assay for estrogen receptor (ER) in the tumor cytosol and thymidine labeling indices (TLI) of 63 primary invasive carcinomas of the breast were analyzed. The ER assay was performed by using dextran-charcoal to adsorb unbound tritiated estradiol-17beta (E2) in cytosol. The TLI was measured as the number per hundred of neoplastic cell nuclei labeled by tritiated thymidine. A significant association between low TLI and presence of ER was found. Wereas all 19 tumors with TLI less than 2.5 contained ER in the primary lesion or in axillary metastases and ER was found in 25 of 30 tumors with TLI between 2.5 and 10, only 4 of 14 tumors with TLI greater 10 contained ER (p less than 0.001). TLI and saturable binding of E2 were significantly negatively correlated (r=-0.436,P. less than 0.001). It is concluded that dedifferentiation in breast carcinomas is associated with both high TLI and absence of ER, and suggested that the carcinomas with the most rapid proliferative rates will include the highest proportion of tumors unresponsive to hormonal therapy.

Juvenile nasopharyngeal angiofibromas (JNA) are rare. They have been frequently treated with estrogens, either solely or as an adjuvant therapy prior to surgery or irradiation. Clinical trials have provided no evidence to explain the objective response to estrogens observed in some tumors. Since the mechanism of steroid hormone action is mediated via specific receptors, we analyzed 8 JNA for tumor cytosol estrogen receptors. None were positive for estrogen receptors. Additionally, all were also negative for progesterone receptors. Nasopharyngeal angiofibromas occur predominantly in adolescent boys at a time when there is a gradual change in androgen availability. Therefore, three latter angiofibromas were also analyzed for the presence of cytosol androgen receptor. Specific testosterone and dihydrotestosterone binding components in the tumor cytosol were detected. This observation raises for the first time the possibility that JNA may be an androgen-dependent tumor. Estrogen may act as an antiandrogen on these tumors, an action similar to that on prostate cancer. Cancer 46:547–551, 1980.

Biochemical study of fibroepithelial tumors of the female breast showed presence of progesterone receptor (PgR) in all five cystosarcoma phyllodes (two malignant, three benign), and in 11 of 13 fibroadenomas tested. Estrogen receptor (ER) was detected in only one of five cystosarcomas and 2 of 13 fibroadenomas. The relative volumes occupied by epithelium and stroma in each tumor were measured from histologic sections. The results were consistent with presence of PgR in the stroma and ER in the epithelium. Different types of cystosarcoma (benign and malignant) and different types of fibroadenomas (intracanalicular, pericanalicular, and mixed) did not differ significantly in content of PgR, and mean levels of PgR in cystosarcoma were comparable with those in fibroadenomas. The presence of PgR in cystosarcomas suggests that progestational therapy, and possibly other forms of hormonal therapy, should be tested in the treatment of advanced, malignant cystosarcoma phyllodes.

Primary renal adenocarcinoma tissue, metastatic deposits, and normal kidney parenchyma from 16 patients were assayed for sex hormone receptors by dextran-coated charcoal adsorption and sucrose gradient centrifugation techniques. Dihydrotestosterone receptors (DHTR) were found in all renal carcinomatous tissue (20/20) and in 93% (13/14) autologous normal kidneys analyzed. Testosterone receptors were found in 84% (16/19) of tumors and 93% (14/15) or normal kidneys analyzed. Estrogen receptors in small amounts (ER) were detected in only 5% (1/19) of tumors and in 7% (1/15) of normal kidneys. Progesterone receptors (PR) in low quantities were detected in 30% (6/20) of renal tumors and in 40% (6/15) of normal kidneys. DHTR levels in high-stage tumors (T3, T4) were significantly elevated over levels in autologous normal kidney, whereas in low-stage tumors localized to the kidney (T1 and T2 tumors) DHTR levels were not significantly different from autologous normal kidney. The mean levels of DHTR in high-stage kidney tumors were significantly elevated over levels in low-stage tumors (P less than 0.001). DHTR estimation in renal neoplasms may help in biologic staging of renal adenocarcinoma and could define a group of patients in whom anti-androgen therapy may be worth a trial.

Fluorescein conjugates to estradiol-17 beta by the sixth carbon (6-FE) and to estrone by the 17th carbon (17-FE) were used to detect estrogen receptors (ERs) in breast cancer tissue sections and in cultured cell lines (human mammary carcinoma MCF-7 and Copenhagen rat prostatic tumor R3327-AT). 17-FE was found to interact with ERs better than 6-FE by biochemical and histochemical techniques. Thin layer chromatography analysis of ethanolic extracts of 17-FE incorporated in tissues and cultured cells showed that over 95% of 17-FE was not metabolized. We concluded that the fluorescence observed in tissue sections and cultured cells was due to 17-FE and not to fluorescein dissociated from the conjugate. Analysis of 65 human breast cancer showed that 74% of the cases were positive for specific 17-FE uptake and 26% were negative. The fluorescence was consistently brighter in the ductal and glandular epithelial cells than in the stroma. specific 17-FE uptake in the nucleoli was observed in MCF-7 and in R3327-AT tumor cells in in vitro cultures, suggesting that these nucleolar estrogen receptors may play a key role in the mechanism of estrogen action. Problems of fluorescence quantitation in tissue sections and cells are discussed.