Estrogen and progesterone receptors in meningiomas

Two-thirds of all meningiomas and four-fifths of intraspinal and sphenoidal meningiomas occur in women. Meningiomas frequently enlarge or become symptomatic during pregnancy or during the luteal phase of the menstrual cycle. There is an increased incidence of meningiomas in women with breast carcinoma. In a series of 23 patients with meningiomas, the authors assayed biopsy specimens of the tumor for the presence of estrogen (ER) and progesterone (PR) receptors, using glycerol density gradient centrifugation and dextran-coated charcoal techniques. Significant levels of ER were found in only 17% of the patients, while significant PR levels were detected in 39%. Only one of the 16 tumors from female patients had significant ER levels, whereas three of the seven tumors from men had significant ER levels. Eight of the 16 tumors in women had significant PR levels, whereas only one of the seven tumors in men had a significant PR level. Thus, three out of four tumors with definite ER were from men, whereas eight of nine tumors with definite PR were from women. Of the eight women whose tumors contained PR, three were premenopausal and five postmenopausal. The single tumor with high levels of PR in the male patient was histologically atypical. The results of this series were compared with six published series of sex steroid assays in meningiomas. These seven series were divided into two groups: one group included two reports from the same laboratories in France, and the other the remaining five reports. Much higher percentages of both ER- and PR-positive tumors were reported from the French group. The authors suggest that this discrepancy may be due to the use of preoperative glucocorticoid therapy in the series from the United States. Since meningiomas are known to enlarge during periods when levels of circulating progestins are high, the presence of significant quantities of PR in a high percentage of tumors may have therapeutic implications for recurrent, malignant, or incompletely excised tumors, or for medically fragile patients. Conversely, since meningiomas are not known to enlarge during the proliferative phase of the menstrual cycle or with exogenous estrogen therapy, the small number of tumors positive for ER may indicate that ER lacks clinical significance. High levels of PR found in a small group of histologically aggressive tumors in several series may indicate that hormonal therapy may be especially useful in this difficult subset of patients.     

Estrogen and progesterone receptors in thyroid lesions

Background: Given the higher incidence and better prognosis of thyroid cancers in women, the possibility arises that these lesions may be influenced by sex hormones. With the development of monoclonal antibodies to the estrogen and progesterone receptor proteins, receptor status can now be determined by immunohistochemical methods that allow direct localization of receptors in tissue. Methods: Using this technique, we have studied tissues of 11 patients, 2 of them pregnant, with thyroid lesions. Paraffin-embedded tissues were used. Positive controls consisted of known estrogen- and progesterone-positive breast carcinomas. Results: Examination of both the thyroid lesions and adjacent uninvolved thyroid tissue showed no nuclear reactivity with either estrogen or progesterone receptor antibodies. Our study did not confirm the previously reported incidence of estrogen and progesterone receptors in thyroid lesions. Conclusions: We conclude that contrary to earlier indications, estrogen and progesterone receptor proteins are neither significantly detectable nor pertinent for follow-up or prognosis in the patient with thyroid neoplasia.The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Navy or the Department of Defense.     

Estrogen and progesterone receptors in gallbladder cancer

Cancerous tissues from 21 patients with primary gallbladder cancer were examined immuno-histochemically for the presence of receptors for estrogen (ER) and progesterone (PGR). ER and PGR, localized in the nucleus, were evident in 52.4 per cent and 0 per cent of the patients, respectively. Furthermore, ER and PGR were positive only in the cytoplasm of cancer cells in 28.6 per cent and 66.7 per cent, respectively. There was a higher tendency of moderately- and poorly-differentiated adenocarcinoma to have an ER-positive rate than well-differentiated adenocarcinoma. With respect to the relationship between ER and sex, ER-positive nuclei were observed in 8 of 14 women (57.1 per cent) and 3 of 7 men (42.9 per cent), but the difference between the two was not significant due to the small number of subjects. These result suggested that gallbladder cancers with ER in the nuclei may respond to antihormone therapy.     

Estrogen and progesterone receptors in gallbladder cancer

Cancerous tissues from 21 patients with primary gallbladder cancer were examined immuno-histochemically for the presence of receptors for estrogen (ER) and progesterone (PGR). ER and PGR, localized in the nucleus, were evident in 52.4 per cent and 0 per cent of the patients, respectively. Furthermore, ER and PGR were positive only in the cytoplasm of cancer cells in 28.6 per cent and 66.7 per cent, respectively. There was a higher tendency of moderately- and poorly-differentiated adenocarcinoma to have an ER-positive rate than well-differentiated adenocarcinoma. With respect to the relationship between ER and sex, ER-positive nuclei were observed in 8 of 14 women (57.1 per cent) and 3 of 7 men (42.9 per cent), but the difference between the two was not significant due to the small number of subjects. These result suggested that gallbladder cancers with ER in the nuclei may respond to antihormone therapy.     

Immunocytochemical evidence of progesterone receptors in human meningiomas

The presence of progesterone receptors in meningioma tissue is demonstrated by use of highly specific monoclonal antibodies against the rabbit progesterone receptors which cross-react with human progesterone receptors in breast cancer cells, thus giving evidence of the existence of genuine progesterone receptors in human meningiomas.     

Estrogen and progesterone receptors in meningiomas: comparison of nuclear binding, dextran-coated charcoal, and immunoperoxidase staining assays

We studied the status of estrogen (ER) and progesterone (PR) receptors in meningiomas removed from 52 patients, comparing dextran-coated charcoal (DCC), nuclear binding (NB), and immunoperoxidase (IP) assays. Each of the assays was performed independently by investigators well-experienced with these assays. The NB assay is a new assay that measures functional steroid receptors--that is, the activation of the receptor and its binding to the nucleus. The assay is very sensitive and requires a relatively small amount of tissue as compared with the DCC assay. In agreement with data from other studies. PR were detected in most meningiomas by all 3 methods: in 69% of the cases by NB, in 76% by DCC, and in 89% by IP. ER were detected in only a few cases: in 33% by NB, in 2% by DCC, and in none by the IP assay. The agreement for PR sites was 62% for all 3 assays; it was 66% between the NB and DCC assays, 67% between the NB and IP assays, and 86% between the DCC and IP assays. Of 26 cases that were positive by the DCC assay, 6 (23%) were negative by NB. The overall agreement for all three ER assays was 65%. The data suggest that the majority of meningiomas contain high-affinity receptors for progesterone, that estrogen receptors are present in only a few meningiomas, and that some of these estrogen and progesterone receptors appear to be functional.     

Estrogen receptor immunoreactivity in meningiomas. Comparison with the binding activity of estrogen, progesterone, and androgen receptors

Estrogen receptor (ER) analysis was performed in 70 meningioma samples by means of two assays: an enzyme immunoassay that used monoclonal antibodies against human ER protein (estrophilin), and a sensitive radioligand binding assay that used iodine-125-labeled estradiol as the radioligand. Low levels of ER immunoreactivity were found in tumors from 51% of patients, whereas ER binding activity was demonstrated in 40% of the meningiomas examined. In eight (11%) of the tissue samples, multiple binding sites for estradiol were observed. The immunoreactive binding sites corresponded to those of the classic high-affinity ER. In ligand binding studies, however, measurement of classic ER was considerably influenced by a second low-affinity high-capacity estrogen binding component, even at low ligand concentrations. Binding activity of the progesterone receptor (PR) and androgen receptor (AR) was determined concurrently using 17 alpha-methyl-3H-promegestone (3H-R 5020) and 17 alpha-methyl-3H-trienolone (3H-R 1881), a synthetic gestagen and androgen, respectively. High concentrations of PR were detected in 53 (76%) of the tumors, whereas a moderate number of AR binding sites were demonstrated in 33 (47%) of the tumors. A positive correlation between ER immunoreactivity and AR binding activity is suggestive of estrogen regulation of AR via the ER system. The presence of gonadal steroid receptors in a large proportion of meningiomas and the tendency toward a dependence of receptor concentrations on the histological subtype of the meningioma could have implications for tumor therapy.     

Estrogen and progesterone receptors in cerebral meningioma and their clinical value

The contents of receptors of steroid hormones (estrogen and progesterone) in cerebral meningioma was studied up. Comparison between this hormones level and mostly significant clinico-morphological characteristics of meningioma was conducted. High frequency of estrogen and progesterone revealing in the tumor tissue permits to suggest the possibility of their application as a test of her hormonal sensitivity and is important for the disease course prognosis and an adequate methods of treatment choice as well.     

Estrogen and progesterone receptors in normal and varicose saphenous veins.

The presence of estrogen and progesterone receptors was investigated in the walls of normal and varicose veins. Cryostat sections from the saphenous veins of 29 normal individuals, and varicose and normal vein segments of 32 patients with varicose veins, were stained with anti-estrogen or anti-progesterone receptor antibodies. Nuclear stain intensity was scored by three independent observers. Receptors to both hormones were detected in the nuclear regions of the intima and media in females and males. In the adventitia, estrogen and the progesterone receptors were found only in nuclei of the vasa vasorum. Estrogen receptor levels were lower in non-varicose segments of varicose veins compared with normal veins. In varicose segments, estrogen receptors were more abundant than in the non-varicose parts of the same vein, especially in females. Similarly, progesterone receptor levels in the non-varicose portions were higher in females. These gender differences may be related to hormonal action. However, these differences may also be age related. These findings may be related to the involvement of sex-hormones in varicosis, by mechanisms as yet unknown.     

Estrogen and progesterone receptors in non small cell lung cancer patients.

The role of sex hormones in the pathogenesis of lung cancer is still unknown. There are conflicting results regarding immunohistochemical detection of the estrogen and progesterone receptors expression in non small cell lung cancer. To clarify these discrepancies 32 samples of lung carcinoma tissues obtained by lobectomy or pneumonectomy were studied. Two monoclonal antibodies (6F11 and ID5) for estrogen receptor detection and one (1A6) for progesterone receptor detection were used. Eighteen adenocarcinoma and 14 squamous cell carcinoma cases were investigated. There were 11 women and 7 men with adenocarcinoma and 4 women and 10 men with squamous cell carcinoma. Weak (+1) nuclear estrogen hormone receptor expression was detected in only one specimen of a woman with adenocarcinoma and in one specimen of a man with squamous cancer. None of the 32 blocks of paraffin embedded specimens expressed progesterone receptor. The positive estrogen and progesterone receptors expression in cancer tissue is an important argument against the pulmonary origin of the unknown primary tumor.     

Progestin receptors in meningiomas

Summary The results are reported of ligand binding and enzyme immunoassays in tumour cytosols, and of immunoperoxidase assays in cryostat and paraffin sections measuring oestrogen (ER) and progestin receptors (PR) in 22 meningiomas and three non-meningioma tumours (two neurinomas and one haemangiopericytoma).With regard to the meningioma tissues, cytochemical immunoperoxidase PR-staining was present in all cryostat sections and in all but one of the paraffin sections. There was a good degree of qualitative accordance between all assay methods; they revealed the picture of typical meningiorna: high PR and low ER.In this series, immunoperoxidase staining for the detection of PR-receptors, both in cryostat and paraffin sections, rendered encouraging results, thus offering a method for the detection of progestin receptors, which can compete with cytosolic methods.     

Simultaneous estradiol and progesterone receptor analysis in meningiomas

The availability of [125I]estradiol and [3H]R5020, a synthetic gestagen, have made it possible to determine estradiol and progesterone receptors simultaneously in 70 meningiomas with a double-labeling assay. With this technique, complete Scatchard analysis can be carried out for both receptors, even with small amounts of tumor tissue such as biopsy specimens. Low levels of estradiol receptor reactivity were found in 11%, whereas specific progesterone receptors were demonstrated in 76%, of the meningiomas examined. No correlation of receptor concentration with sex or age of the patients or with location of the tumor has yet been demonstrated. However, indications of a correlation between gestagen binding activity and histological subtypes were found. The presence of progesterone receptors in a large proportion of meningiomas could have implications for tumor therapy.     

Sex steroid receptors in human meningiomas

Results of experiments on the presence of steroid receptors in a series of 67 meningioma tissues, which were derived from 64 patients are presented. All tissues were studied using dextran-coated charcoal adsorption and Scatchard plot analysis. Progestin receptors were present in a high concentration in more than 80% of the specimens. Very low concentrations of an oestrogen binding agent were found in a limited number of samples. Thus, most meningiomas contain high levels of progestin receptors in the virtual absence of oestrogen receptors. Relations were not observed between progestin receptor-content and the age and sex of the patients, or the location and the histological type of the tumour. The role and action of progestin on meningiomas is still unknown. The presence of progestin receptors, however, suggests that meningioma may be regarded as a true target tissue for progestins.     

Estrogen and progesterone binding sites in renal cell carcinoma

Twenty-five renal cell carcinomas were assayed for estrogen and progesterone receptor levels. Estrogen specific binding was present in only 4 patients (16%) and progesterone specific binding in 7 patients (28%). In all cases these receptors were present in very low titers, less than 10 fm/mg. We believe that earlier reports citing significant estrogen and progesterone binding activity may reflect high levels of nonspecific protein binding.     

Estrogen receptors in acoustic neurilemmomas

Acoustic neurilemmomas are more frequent, larger, and more vascular in women, and such lesions have a rapidly progressive clinical course in pregnant women; these findings suggest that the growth of these neoplasms may bear a relationship to certain hormone levels. Tissues from 8 patients with acoustic neurilemmoma (3 men and 5 women) were studied by a new fluorescent steroid histochemical technique to detect the presence of estrogen receptors in or on neoplastic cells. Estrogen receptor protein has also been found in meningioma cells in women. Neurilemmoma of the acoustic nerve is the second neoplasm of the central nervous system in which such receptors have been demonstrated.     

Estrogen receptors in breast cancer

Of 1100 women whose primary and/or metastatic breast cancers have been analyzed for estrophilin, 30% are receptor-rich and 70% receptor-poor. On the basis of 134 treated patients, nearly two-thirds of the receptor-rich group can expect objective benefit from endocrine therapy, whereas few if any of the receptor-poor patients will respond. Thus, estrophilin assay indicates the proper type of therapy for 85 to 90% of women with advanced breast cancer. Analysis of the primary tumor in the mastectomy specimen offers promise in predicting hormone dependency in metastases that appear up to 5 years later.

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Résumé Chez 1100 femmes, la tumeur mammaire primitive et/ou des métastases ont été testées pour la présence de récepteurs d'oestrogènes: 30% sont riches en récepteurs, 70% sont pauvres. D'après l'expérience de 134 malades traitées, on peut s'attendre à une réponse objectivement favorable à l'hormonothérapie dans prè des 2/3 du groupe riche en récepteurs. Pour le groupe pauvre en récepteurs, il n'y a que peu ou pas réponse. La détermination des récepteurs d'oestrogène indique donc le traitement adéquat dans 85–90% des cancers du sein au stade avancé. L'analyse de la tumeur enlevée par mastectomie permet de prédire l'hormonodépendance des métastases qui apparaÎtraient jusqu'à 5 années plus tard.

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This investigation was supported by USPHS Contract N01 CB-43969 and Grant 5 P01 CA-24599.     

Estrogen and progesterone binding by acoustic neuroma tissue

Tissue samples from 37 acoustic neuromas were assayed for estrogen and progesterone hormone receptor binding by radioimmunoassay using a dextran-coated charcoal method and Scatchard plot analysis. Twenty-one of the samples were from men, and 16 of the samples were from women. Seven of 37 samples (19%) were positive for estrogen receptor and six of 36 samples (17%) were positive for progesterone receptor. Three of 37 samples (8%) were positive for both receptors. There was no correlation of estrogen receptor positivity with the sex of the patient. These results indicate that estrogen or progesterone receptor binding activity or both are present in a small subset of acoustic tumors. Evidence is lacking, however, that binding of estrogen to the receptor results in growth changes in the tumor. The empirical use of antiestrogen treatment in acoustic neuroma does not appear to be justified at the present time.