Uniones específicas a estradiol y progesterona en meningiomas y neurinomas: correlación clínica y con el edema cerebral / Specific binding of estrogen and progesterone in meningiomas and neurinomas: relation to clinical features and brain edema

El predominio de meningiomas (M) en el sexo femenino, la exacerbación de los sintomas durante el embarazo y el mayor grado de crecimiento de los neurinomas (N) en la edad fértil en mujeres sugieren la posible hormonodependencia de estos tumores. Se estudiaron 16 M, pertenecientes a 7 hombres y 9 mujeres y 5 N de mujeres, obtenidos quirúrgicamente y conservados en nitrógeno líquido. Se determinó en ellos la densidad de receptores (R), de acuerdo a la unión específica a estradiol (E) y progesterona (P), con técnica de Carbón Dextrán. Se consideraron positivos valores mayores a 10 fentomoles de hormona unida por miligramo de proteína citosoluble. Se midió además el grado de edema cerebral de los M en la TAC y se lo expresó como el porcentaje de edema cerebral, en relación al parénquima cerebral no comprometido por edema. Once de 16 M tuvieron R positivos para E y 8 de 16 para P. Tres de 5 N tuvieron R positivos para E y 2 de 5 para P. Si bien un 66,6%de los tumores presentaron R a E y 47,6%R a P, no pudo encontrarse relación entre ellos y la edad , sexo, estado menopáusico de las pacientes ni tipo histológico de los tumores. Tampoco se encontró correlación estadísticamente significativa entre el porcentaje de edema y el nivel de R a E y P en los M evaluados. Nuestros resultados evidencian que un alto porcentaje de M y N presentan R positivos a E y P. Desconocemos el significado funcional de los mismos y la falta de correlación con el grado de edema peritumoral no permite relacionar su presencia con la generación del mismo

Uniones específicas a estradiol y progesterona en meningiomas y neurinomas: correlación clínica y con el edema cerebral / Specific binding of estrogen and progesterone in meningiomas and neurinomas: relation to clinical features and brain edema

El predominio de meningiomas (M) en el sexo femenino, la exacerbación de los sintomas durante el embarazo y el mayor grado de crecimiento de los neurinomas (N) en la edad fértil en mujeres sugieren la posible hormonodependencia de estos tumores. Se estudiaron 16 M, pertenecientes a 7 hombres y 9 mujeres y 5 N de mujeres, obtenidos quirúrgicamente y conservados en nitrógeno líquido. Se determinó en ellos la densidad de receptores (R), de acuerdo a la unión específica a estradiol (E) y progesterona (P), con técnica de Carbón Dextrán. Se consideraron positivos valores mayores a 10 fentomoles de hormona unida por miligramo de proteína citosoluble. Se midió además el grado de edema cerebral de los M en la TAC y se lo expresó como el porcentaje de edema cerebral, en relación al parénquima cerebral no comprometido por edema. Once de 16 M tuvieron R positivos para E y 8 de 16 para P. Tres de 5 N tuvieron R positivos para E y 2 de 5 para P. Si bien un 66,6%de los tumores presentaron R a E y 47,6%R a P, no pudo encontrarse relación entre ellos y la edad , sexo, estado menopáusico de las pacientes ni tipo histológico de los tumores. Tampoco se encontró correlación estadísticamente significativa entre el porcentaje de edema y el nivel de R a E y P en los M evaluados. Nuestros resultados evidencian que un alto porcentaje de M y N presentan R positivos a E y P. Desconocemos el significado funcional de los mismos y la falta de correlación con el grado de edema peritumoral no permite relacionar su presencia con la generación del mismo

Meningeoma justa-selar / Juxta-sellar meningeoma

Meningeomas intracranianos säo tumores frequentes e a localizaçäo justa-selar ocupa o quinto lugar como origem. Podem crescer dentro da sela, mas raramente säo apenas intra-selares e geralmente apresentam importante crescimento supra-selar. O diagnóstico tardio desses tumores pode tornar as alteraçöes visuais e endócrinas irreversíveis, aumentando a morbidade e mortalidade. O diagnóstico precoce pode ser realizado com a tomografia computadorizada do crânio e da regiäo selar, com contraste paramagnético. Neste trabalho säo apresentados 4 pacientes portadores de meningeoma justa-selar que tinham como principal queixa a perda progressiva da visäo

Meningeoma do clivo: relato de um caso / Clivus meningeoma: a case report

Os autores apresentam um caso de meningeoma do clivo operado por via oral. O caso foi estudado previamente por todos os métodos radiológicos: radiografias simples de crânio e coluna, tomografia axial computadorizada, mielografia cervical e ressonância magnética. Somente com este último método foi possível o diagnóstico topográfico da lesäo e aventada a hipótese de meningeoma

Multiparameter flow cytometric analysis of neoplasms of the central nervous system: correlation of nuclear antigen p105 and DNA content with clinical behavior.

Analysis of the DNA content of various solid tumors and hematological malignancies may provide useful prognostic information. To date, however, there has been a striking lack of correlation between DNA content in neoplasms of the central nervous system and clinical behavior. Simultaneous quantitation of DNA content and proliferation-associated nuclear antigen (p105) by flow cytometry was performed on paraffin-embedded tissues representing three major groups of central nervous system neoplasms--1) 21 astrocytic tumors, 2) 13 pituitary tumors, and 3) 19 meningiomas--and the results were correlated with clinical behavior. All 4 well-differentiated gliomas were diploid, while 3 of 9 anaplastic astrocytomas and 1 of 8 glioblastomas had a demonstrable aneuploid peak. Three of 13 pituitary tumors had an identifiable aneuploid peak, while only 2 of 19 meningiomas had an aneuploid DNA content. Cell-cycle analysis of the malignant gliomas revealed a significantly higher proliferative index (PI, %S + G2M) compared with the well-differentiated astrocytomas (P less than 0.05). Within the subgroup of diploid anaplastic astrocytomas, however, extended patient survival appeared to be associated with a higher PI. For diploid pituitary adenomas, the PI was consistently lower in the 3 tumors that recurred than it was in the remaining 8 adenomas. Nuclear antigen quantitation of diploid tumors showed a wide range of p105 expression in G0G1 cells, suggesting that, within each tumor, the cells are heterogeneous with respect to proliferative activity. Aneuploid nuclei of glial tumors showed enhanced expression of p105 relative to diploid cells of the same specimen. In pituitary tumors, the median G2M/G0G1 fluorescence ratio for p105 was significantly higher (P less than 0.05) for the 3 diploid recurrent tumors than for those that did not recur. These data support the assumption that the aggressive clinical course of malignant glial neoplasms may be related to an abnormal DNA stemline and/or an alteration in cell proliferative activity. Cell cycle analysis and measurement of p105 by this technique may provide information useful from both a prognostic standpoint and in directing adjuvant therapy.

Identification of gonadal steroid receptors in meningiomas from dogs and cats.

Cytosolic assay was used to detect gonadal steroid receptors in brain tumor tissue from 6 dogs and 2 cats. For 4 samples, the maximal number of binding sites and the equilibrium dissociation constant were calculated, using Scatchard analysis. The concentration of receptor protein that was discovered was similar to that detected in hormone-sensitive tumors.

Sex steroids in human brain tumors and breast cancer.

The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor and breast cancer tissues. The concentrations in malignant gliomas and breast cancers showed interindividual variations, especially evident with regard to estradiol. High estradiol concentrations were recorded in two patients with malignant astrocytoma. The concentrations of 1.00 pg/mg and 3.32 pg/mg were 10 to 30 times as high as in normal female brain. In five of ten astrocytomas the estradiol concentration was higher than the lowest breast cancer value. The distribution of progesterone seemed more even, and the level was significantly lower in brain tumors and breast cancers as compared with female brain, perhaps indicating an increased metabolism. Testosterone levels were somewhat higher in brain tumors, as compared with breast cancers, but not different from values in brain tissue. There were no significant age or sex correlation or differences in the concentrations of steroids in the brain tumors. The results suggest that manipulation of sex steroid metabolism in malignant brain tumors can be of beneficial therapeutic value as has been shown for breast cancer and prostatic carcinoma.

Histological, ultrastructural and chromatographical discrimination of phospholipids in meningiomas.

Phospholipids in meningiomas were studied by light and electron microscopy, and by high-performance liquid chromatography. They were microscopically demonstrated in six of the ten cases by Sudan III staining after the fixation with potassium dichromate. However, the conventional ultrastructural fixation with glutaraldehyde and osmium tetroxide failed to confirm phospholipids, as most of them were dissolved during dehydration. In contrast, the specimens pretreated with tannic acid before osmication ultrastructurally retained phospholipids which were represented by multilamellar bodies or ribbon-like rings. Both were found in 23 of the 30 cases within the cytoplasm, among the plasma membranes and in the extracellular matrices. The outermost lamella or ribbon showed a direct continuity from the neighbouring plasma membranes of the cytoplasm or the mitochondria. The multilamellar bodies showed an overall distribution, while the ribbon-like rings were predominantly distributed around the psammoma bodies. Precipitation of hydroxyapatite crystals within the ribbon-like rings resulted in matrix minerals of psammoma bodies. Chromatographical analyses of meningiomas disclosed phospholipids including phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine, sphingomyelin and phosphatidyl inositol in that order. Psammomatous meningiomas contained a higher percentage of phosphatidyl serine than non-psammomatous tumors. Ultrastructural study of synthetic phospholipids adequately treated with tannic acid showed that the multilamellar bodies were similar to phosphatidyl choline, while the ribbon-like rings were similar to phosphatidyl serine. The role of phospholipids in meningiomas is discussed.

[Differential immunohistochemical characteristics of meningiomas and other neoplasms of the central nervous system]. / Características inmunohistoquímicas diferenciales de los meningiomas con otras neoplasias del S.N.C.

We present an immunohistochemical study of 16 meningiomas and 19 CNS tumors including gliomas, neurinomas and metastatic carcinomas, in order to establish a histopathologic differential diagnosis, using formalin-fixed and paraffin-embedded material. The antibodies analysed included vimentin, GFA-protein, cytokeratin, S-100 protein and epithelial membrane antigen. Meningiomas always express vimentin as marker, and occasionally cytokeratin and EMA. The most constant antigens demonstrated in astrocytomas were GFA-protein and vimentin, and occasionally we were able to detect S-100 protein. Neurinomas proved positive to S-100 protein, and metastases presented cytokeratin and EMA reactivity. Our results confirm the existence of diverse immunohistochemical patterns within CNS tumors, a fact that can be useful in routine differential diagnosis.

Steroid hormone and epidermal growth factor receptors in meningiomas.

A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

Epithelial differentiation in meningiomas. An immunohistochemical, histochemical, and ultrastructural study--with review of the literature.

Meningiomas possess features indicative of epithelial differentiation. The present study further documents this finding by a multimodality approach on serial sections from 25 meningiomas of all histologic and clinical categories. Standard light microscopic examination, immunohistochemical staining with a variety of epithelial and nonepithelial markers, and histochemical staining for mucin were performed on each case. Directed electron microscopic examination was performed on selected examples of epithelial feature-positive and -negative cases. All cases were immunoreactive for vimentin and epithelial membrane antigen. Thirty-two percent were reactive for cytokeratin and 39% for S-100. Twenty percent showed mucin positivity by histochemistry. Electron microscopic examination of cytokeratin-positive cases showed either intracellular lumina (secretory areas) or cytoplasmic tonofibrils, whereas cytokeratin-negative tumors lacked lumina and tonofibrils. Previous studies showing epithelial features in meningiomas are reviewed with emphasis on the studies using immunohistochemistry. These histochemical, immunohistochemical, and ultrastructural characteristics are of utility in the examination of tumors of suspected meningeal origin, particularly when dealing with atypical presentations or histomorphologic features.

[Behavior of estrogen and progesterone receptors in intracranial meningioma]. / Osservazioni sul comportamento dei recettori per gli estrogenied il progesterone nel meningioma intracranico.

Observation on value of estrogen and progesterone receptors in intracranial meningiomas. The authors take into consideration twenty intracranial meningiomas reperted in patients that differ for age, sex and histological pattern of the lesions, for value receptor content and their variability with mentioned variants. They report receptors contents of meningiomas and its variability with age and histological pattern.

Ganglioside composition in human meningiomas.

The ganglioside composition in meningioma specimens from 20 patients was analyzed to find potential meningioma-associated structures. The characterization was performed by immunological staining with specific monoclonal antibodies to ganglioside antigens and fast atom bombardment-mass spectrometry. The major gangliosides were GM3 and GD3, and most of the meningioma specimens could be divided into a "GM3-rich" or a "GD3-rich" group. Gangliosides of the gangliotetraose series were represented by GM1, GD1a, GD1b, and GT1b, which were found in minor amounts in all the specimens. The ratios of GM1/GD1a and GD1a/GD1b differed from that in normal brain, and therefore existence of this series could not be explained by contamination with brain material. Ganglioside 3'-isoLM1, found in human malignant glioma, could not be detected in any meningioma specimen.

Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: initial experience in patients with cerebral tumors.

A recently developed method for image-selected localized hydrogen-1 magnetic resonance (MR) spectroscopy was assessed in the differential diagnosis of nine primary and secondary cerebral tumors, including four gliomas, two meningiomas, one neurilemoma, one arachnoid cyst, and one metastasis of breast cancer. Well-resolved H-1 MR spectra of these tumors were obtained in vivo with a conventional 1.5-T whole-body MR imaging system. All tumor spectra were remarkably different from spectra from normal brain tissue. Spectra obtained from different tumors exhibited reproducible differences, while histologically similar tumors yielded characteristic spectra with only minor differences. The observed spectral alterations reflect variations in concentrations and relaxation times of the H-1 MR sensitive pool of free (mobile) metabolites within the tissues. In most cases, the concentrations of N-acetyl-aspartate and creatine/phosphocreatine are reduced below detectability, whereas choline-containing compounds are generally enhanced. The spectral differences between the tumors are mainly due to the differing concentrations of lipids, lactic acid, and carbohydrates. Localized H-1 MR spectroscopy may become an important clinical tool for the differentiation of tumors as well as for therapeutic control.

Two-dimensional electrophoretic analysis of nuclear proteins from human tumors.

During the last decade several strategies have been developed to identify proteins which could serve as markers in tumor biology. One avenue of great promise to detect such proteins seems to be the separation of prefractionated organelles from tumor cells by high resolution two-dimensional electrophoresis. Using detergent-lysed nuclei from several human tumor cell lines, especially from brain tumors, and two-dimensional electrophoresis, we analyzed the nuclear protein pattern obtained after sequential salt extraction of tumor cell nuclei. In addition to proteins occurring in all tumor cell lines, the pattern of different tumor cell lines exhibits considerable differences when proteins were visualized by silver staining, thus emphasizing the specificity of nuclear proteins with respect to the cell type. Even quantitative variations of the nuclear phosphoproteins 23/4 were detectable, indicating a potential correlation between their synthesis/phosphorylation and the proliferation behavior of tumor cells. The data indicate that nuclear proteins with their distinct heterogeneity and tissue specificity may represent a powerful source in determining tumor-specific proteins. The extent of chromosomal protein heterogeneity may be additionally increased by their covalent modification by nuclear kinases; therefore, tumor-specific nuclear proteins may occur as quantitative and qualitative variations.

Calmodulin content in human central nervous system tumors.

Benign and malignant brain tumors and normal cerebral cortex were assayed for calmodulin content by enzymatic and radioimmunoassay techniques. Normal cerebral cortex contained more (8.31 +/- 1.27 vs 3.30 +/- 0.42 micrograms/mg protein) calmodulin than the brain tumors. The contents of calmodulin in the malignant glioblastomas were significantly higher than the meningiomas (5.41 +/- 0.31 vs 2.97 +/- 0.16 micrograms/mg protein). These differences were independent of tumor location and persisted when calmodulin content was normalized for DNA rather than protein content. This data supports differences in the tissue calmodulin contents with normal cortex greater than primary malignant tumors greater than benign tumors greater than metastatic tumor tissue.

[Immunohistochemical study of c-myc oncogene product in human brain tumors].

C-myc oncogene is widely distributed in eukaryotic cells and is supposed to play an important role in the cellular proliferation and differentiation. Enhanced expression of this oncogene is reported in many kind of tumors, which is often associated with increased malignancy. It seems, therefore, important to study the expression of this oncogene in analyzing the cell biologic features of brain tumors. In the present paper we investigated the distribution of this oncogene product in paraffin-embedded tissue of various kind of brain tumors with a monoclonal antibody to synthetic c-myc peptide. The results demonstrated that c-myc product was detectable in most of the astrocytoma lineage. The immunoreaction within the cell nuclei was more intense in grade 3 and grade 4 astrocytomas than in grade 2 tumors. The expression in grade 4 tumors was, however, rather weaker that in grade 3 tumors. In benign, non-glial tumors like meningiomas and neurinomas, the nuclear immunoreaction was usually absent or only weak, although it was enhanced in a case of acoustic and spinal neurinomas associated with von Recklinghausen's disease.

Rapid growth of a meningioma during pregnancy: relationship with estrogen and progesterone receptors--case report.

Meningiomas are often described as hormone-dependent because of their preponderance in females and their tendency to clinically manifest during or after pregnancy. We describe a case of meningioma that grew rapidly during two pregnancies over a 2-year period. The tumor's rapid growth was confirmed by high-resolution computed tomography. Its estimated doubling time was 110 days. The tumor was removed and found to be a benign meningothelial meningioma. The tumor tissue was positive for estrogen receptors (ERs) and progesterone receptors (PRs). In nine cases, including this one, in which ERs and PRs were measured, the positive rate was much higher for PRs than for ERs; only two were positive for ERs. In the case reported here, it is presumed that the growth of the meningioma was influenced by estrogen and/or progesterone binding to receptors, although it is unclear whether one or both hormones was involved.