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Fifty meningiomas of four major histological types have been examined by immunocytochemical methods applied to formalin fixed paraffin embedded material and using readily available commercial antisera. The expression of GFAP, S100, NSE, vimentin, cytokeratin, fibronectin and desmoplakin was investigated. The majority of tumours contained NSE (86%) and S100 (78%), and all irrespective of histological type, contained vimentin and fibronectin. The epithelial marker cytokeratin was found in 56% of cases, but showed only focal expression. The relevance of these findings to histogenesis and metabolism is discussed and it is suggested that intermediate filament typing provides valuable information on meningiomas structure and function. The possible role of NSE and S100 in meningeal neoplasm is discussed.

Polyamine levels have been studied in brain tumor patients. We focused our study on the relationship between tumor, cerebrospinal fluid (CSF) and red blood cell (RBC) polyamine levels. Our results are the following: Polyamine levels in CSF are consistently increased, whatever the histological type may be. The highest tumoral concentrations are found in medulloblastoma. In glioblastomas, the RBC spermidine levels are higher than in the other types of tumors and there is a highly significant correlation between the spermidine/spermine ratio in tumor and RBC. Therefore, RBC polyamine determination might be of clinical interest in the monitoring of patients with glioblastomas.

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.

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.

Progestin receptors (PR) were evaluated in 40 intracranial and 2 spinal meningiomas. PR measured with radiolabelled R 5020 were found in 93% of cases (39/42). PR levels were significantly higher (p = 0.05) in females (mean: 5,720 fmol/gmT) than in males (mean: 3,120 fmol/gmT). Biochemical characterization of the R 5020 saturable binding sites showed that they were mainly cytosolic, had a high affinity constant (Kd approximately equal to 1 nM) and were progestin specific. Correlation with sex suggested some biological activity of PR in meningiomas. Oestrogen receptors (OR) were evaluated in 36 intracranial and 2 spinal meningiomas. OR measured with radiolabelled R 2858 were present in 79% of cases (30/38). OR mean levels were equal in females (mean: 285 fmol/gmT) and in males (mean: 330 fmol/gmT). The relevance of PR and possibly OR in the biology of meningiomas and of leptomeninges was suggested by the presence of receptors in a sample of normal leptomeninges.

Progestin, estrogen, androgen, glucocorticoid as well as mineralocorticoid receptors (PR, ER, AR, GR and MR, respectively) were all evaluated with specific synthetic radioligands (biochemical assays) in 25 meningiomas, 9 gliomas and 4 brain metastases. In meningiomas the main steroid hormone receptors appeared to be the progestin receptor, present in 24/25 cases (mean level: 7 105 fmol/gT) and the androgen receptor, present in 23/25 cases (mean level: 2 265 fmol/gT). Progestin receptor levels were found to be significantly lower in meningiomas of the fibroblastic subtype whereas none of the steroid hormone receptors were detected in the anaplastic case. On the other hand, glucocorticoid receptor levels were related to the preoperative glucocorticoid therapy. In gliomas only estrogen receptors (2/9 cases) and especially androgen receptors (8/9 cases) were noticeable: the latter seemed to be related to the histological types and to the sex of patients. No receptors were found in any of the four studied metastases, including one from breast cancer. The biochemical characterization of the receptors as well as their relevance to tumor biology and to the physiology of the normal tissues where tumors arise, were discussed, and biochemical data were compared with those previously reported.

Medroxyprogesterone acetate (MPA) has been used in high doses as hormone treatment for metastatic breast cancer. We treated five intracranial meningiomas with MPA expecting that MPA would reduce the volume or decrease the growth rate. All five patients were postmenopausal women, aged 47 to 73 years. Before treatment, the growth rate of each tumour was assessed by two consecutive CT scans (CT 1 and CT 2). Tumours 1 to 4, histologically benign meningiomas, grew slowly as the tumour volumes were not found to increase in 21 to 45 months between CT 1 and CT 2. Tumour 5 was an anaplastic meningioma the rapid growth of which was evident in 8 weeks between CT 1 and CT 2. After CT 2, MPA was given 1,000 mg intramusculary once weekly for 17 to 29 weeks until CT 3 which showed the response. Tumours 1 to 4 had neither reduced in volume nor developed necroses, and tumour 5 continued its fast growth at the same rate as before.