Lectin binding pattern in meningiomas of various histological subtypes

Altered tumour cell glycosylation in relation to cellular heterogeneity in human brain tumours remains relatively unexplored. It has been reported that meningiomas express variability in glycosylation properties; however only limited meningioma subtypes have been studied with lectins histochemistry. The aim of this study was to compare the binding pattern of biotinylated lectins in seven subtypes of histologically benign intracranial meningiomas (meningothelial, transitional, fibroblastic, psammomatous, secretory, microcystic and angiomatous types). The study was performed on biopsy material of 30 cases of meningiomas with different lectins: Peanut agglutinin (PNA), Soybean agglutinin (SBA), Dolichos biflorus agglutinin (DBA), Wheat germ agglutinin (WGA), Cocanavalin A (Con A) and Ulex europaeus agglutinin 1 (UEA-1). The expression of lectin-binding glycoconjugates exhibited differences between certain subtypes of meningiomas. WGA with affinity for GlcNAc and neuraminic acid labelled the cells of all meningiomas but most intensely those of fibroblastic type. Staining with PNA, SBA and DBA, which are GalNAc specific, varied from negative to strongly positive. Enhanced PNA reactivity reflected mainly cytoarchitectural pattern of tumour growth, such as syncytial lobules, whorled formations or trabecular arrangements of meningioma cells. DBA labelled the majority of cellular nuclei. SBA showed binding to psammoma bodies, while pseudopsammoma bodies were stained with PNA, WGA, Con A, and to a lesser extent with SBA and DBA. The secretory meningiomas exhibited strong and heterogeneous lectins reactivity within pseudopsammoma bodies whereas the neoplastic cells were only occasionally stained. The selective reactivity of UEA-1 with endothelial cells of blood vessels resulted in a specific visualisation of the vascular network in all histological subtypes of meningiomas. These results documented the heterogeneous glycosylation pattern in different subtypes of meningiomas and indicate the usefulness of lectins in the evaluation of pluripotential differentiation of meningioma cells.     

LECTIN BINDING IN MENINGIOMAS

Forty-two meningiomas of different morphological sub-type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub-types of meningioma to be distinguished although the biological significance of the binding patterns is unclear.     

Cell‐adhesion molecules in human meningiomas: correlation with clinical and morphological data

Integrins form a family of cell adhesion molecules. CD44 glycoproteins are found in a wide variety of isoforms; the most common, CD44s (standard) is widely distributed, and functions as an adhesion molecule. In this study, we have investigated immunohistochemically the distribution of some VLA integrins (α2, α5 and α6 chains of β1 integrins) and CD44s in 44 meningioma specimens and normal arachnoid villi. Meningiomas were of meningothelial (16), transitional (13) and fibroblastic (15) subtypes. There were 13 grade I, 19 grade II and 12 grade III (27%). Immunoprecipitates were quantified by image analysis and correlated with clinical (age, sex, location) and morphological data (histological subtypes and grades). VLA α5 chain was expressed by normal arachnoid villi (mainly cap cells) and by 42 out of 44 meningioma specimens. Expression was lower in fibroblastic meningiomas (P=0.02). VLA α2 and α6 chains were not observed in normal arachnoid villi. VLA α2 was expressed by 15 meningiomas, VLA α6 by 10. Interestingly, meningiomas expressing either VLA α2 or α6 were usually of grade III (P≤0.05). CD44s was found on various parts of arachnoid villi and in all meningiomas although expression was higher in meningothelial and transitional than in fibroblastic (P≤0.001). These results show that VLA α5 and CD44s are widely expressed by arachnoid villi and meningiomas, in contrast to VLA α2 and VLA α6. It was noted that high grade meningiomas (III) express VLA α2 and α6 suggesting that changes in integrin pattern expression are a feature of these meningiomas. Moreover, strong CD44s expression characterizes meningothelial and transitional meningiomas. Previous studies have shown that high NCAM expression is a feature of fibroblastic meningiomas whereas meningothelial and transitional meningiomas expressed mainly E-Cadherin, and that polysialylated NCAM expression was restricted to high grade meningiomas. Taken together these features suggest that each cell adhesion molecule has a characteristic pattern of expression according to meningioma subtype and grade. No correlation was seen between integrins and CD44s expression and clinical data.     

The double immunostaining of CD133 and Ki-67 favours a significant co-localization pattern in fibroblastic subtype of meningiomas

BACKGROUND AND PURPOSE : A unique molecular and/or cellular marker for meningiomas, the most common intracranial tumours, has not been identified yet. MATERIAL AND METHODS: We investigated the co-localization fraction of CD133/Ki-67 in meningioma tissue array slide composed of 80 meningioma tissue samples of various histological variants. CD133 - a cell membrane stem cell marker - was previously proved to be associated with the initiation and progression of intracerebral gliomas and medulloblastomas. RESULTS : Immunohistochemical co-localization of CD133/Ki-67 was significantly higher in fibroblastic variant than in meningothelial and transitional subtypes. However, since there were only 3 atypical and 1 malignant meningioma spots in the tumour tissue array slide, it is difficult to draw a firm conclusion regarding the actual co-localization percentage and persistence of CD133/Ki-67 in atypical and malignant meningiomas. CONCLUSIONS : Far higher co-staining percentage of CD133/ Ki-67 in fibroblastic meningioma samples compared to meningothelial subtype, a histological meningioma variant, architectonically resembling the non-neoplastic meningeal cells, gave us the impression that CD133 may play a role in the formation and progression of fibroblastic meningioma variants. The persistency and the validity of this finding need to be verified by further histopathological and molecular research in order to clarify the possible role of CD133 in meningiogenesis.     

Patterns of SPARC expression and basement membrane intactness at the tumour-brain border of invasive meningiomas

The matricellular glycoprotein SPARC (secreted protein, acidic and rich in cysteine), also termed osteonectin, has been found to regulate the invasive behaviour of several tumour types by interacting with basement membrane constituents. Brain invasive meningiomas are supposed to disrupt the pial-glial basement membrane. In the present study we aimed at determining the relationship of basement membrane intactness and SPARC protein expression at the meningioma-brain border. Sections of 51 brain-invasive meningiomas (31 meningothelial meningiomas WHO grade I, 11 atypical WHO grade II, and nine anaplastic WHO grade III tumours) were immunolabelled with antibodies against SPARC, epithelial membrane antigen (EMA), collagen IV and glial fibrillary acidic protein (GFAP). Twenty-two non-invasive WHO grade I meningothelial meningiomas were included in the study for comparison. At the tumour-brain border of invasive meningiomas, spindle-shaped tumour cells expressed SPARC. The number of tumours containing SPARC+ spindle cells did not differ significantly between WHO grades. By contrast, the number of WHO grade I tumours expressing collagen IV (15/31) was highly significantly elevated when compared with WHO grade II (1/11) and WHO grade III (0/9) (both P < 0.0001). There was an inverse relationship of the presence of SPARC+ spindle cells and basement membrane material. In conclusion, the destruction of the basement membrane is correlated with meningioma malignancy grade whereas the expression of SPARC protein at the tumour-brain border is not. Destruction of the basement membrane and appearance of SPARC+ spindle cells are not coincident during the course of brain invasion by meningiomas.     

Glycoprotein pattern in human brain tumors studied using lectin binding after sodium dodecyl sulfate-gel electrophoresis and protein blotting

The immunoblotting technique was used to study the glycoproteins in human brain tumor samples including astrocytoma, glioblastoma, meningioma and oligodendroglioma, as well as in normal human brain. Glycoproteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electrophoretically transferred to nitrocellulose membrane and characterized, using binding with 11 different lectins. Tumor-associated glycoproteins were found using the lectins peanut agglutinin (PNA), soybean agglutinin, Limulus polyhemus, Lotus tetragonolobus, Ricinus communis 1, (RCA-1) and wheat germ agglutinin (WGA). Their molecular masses ranged from 50 to 180 kDa. Several of them were common to the 3 types of tumors: astrocytomas, oligodendrogliomas and meningiomas. PNA, RCA-1 and WGA were the 3 most feasible lectins with regard to tumor specificity, simplicity and reproducibility.     

Invasive meningioma is associated with a low expression of E-cadherin and beta-catenin

Invasive meningioma shows benign histological features (WHO grade 1) and the brain expansion at the tumor-brain interface, and recurs more frequently than common meningiomas. To determine the mechanism of brain expansion, we studied the relationship between invasive meningioma and cell adhesion molecules. Immunostaining for E-cadherin (E-CH), N-cadherin (N-CH), beta-catenin, and Ki-67 was performed in 103 meningiomas that consisted of 61 meningothelial meningiomas, 25 fibrous meningiomas, 12 invasive meningiomas and 5 anaplastic meningiomas. All tumors were negative for N-CH. All the 61 meningothelial meningiomas, 10 of 12 invasive meningiomas, and 3 of 5 anaplastic meningiomas were positive for both E-CH and beta-catenin, while these were both negative in all of the fibrous meningiomas. In invasive meningiomas, the expansive part of the tumor showed a lower rate (4/12 tumors) of E-CH and beta-catenin positivity, while the central part showed a higher rate (10/12 tumors). The Ki-67 labeling index was higher in invasive and anaplastic meningiomas than in meningothelial meningiomas. These results suggest that a reduction in cell adhesion molecules and increased proliferative activity may be related, which may lead to a better understanding of the mechanism of meningioma expansion in the future.     

The astrocytic response towards invasive meningiomas

meningiomas disrupt the pial-glial basement membrane. This membrane is closely attached to the subpial glial endfeet forming the glia limitans. The fate of subpial astrocytes during the course of brain invasion by meningiomas is not known. In the present study we immunolabelled sections of 35 brain-invasive meningiomas (14 meningothelial meningiomas WHO grade I, 11 atypical WHO grade II and 10 anaplastic WHO grade III) using anti-collagen IV to label basement membrane material, and antibodies against astrocytic markers CD44, SPARC (secreted protein, acidic and rich in cysteine) and glial fibrillary acidic protein (GFAP). Astrocytes were present at the tumour-brain interface of 14/14 WHO grade I meningiomas, 9/11 WHO grade II tumours and 9/10 WHO grade III tumours. The presence of astrocytes was associated with an intact basement membrane in 11/14 WHO grade I meningiomas (P < 0.01), 6/9 WHO grade II tumours, and 6/9 WHO grade III tumours. However, tumour embedded in deep brain parenchyma lacked both an astrocytic reaction and basement membrane material. In conclusion, astrocytes eventually disappear from the tumour-brain interface during the course of meningioma infiltration. This observation might indicate that the survival of subpial astrocytes is dependent on an intact pial-glial basement membrane.     

Sclerosing meningioma: immunohistochemical analysis of five cases

Sclerosing meningioma is a rare morphologic subtype of meningioma and may be mistaken for atypical or malignant meningioma and astrocytoma or schwannoma because of marked collagen deposits and a sparse population of cells with little resemblance to meningothelial cells. Authors describe the histopathologic and immunophenotypic features of five cases of sclerosing meningioma. Histologically, all the cases consisted of paucicellular collagenous tissue containing spindle cells with or without small foci of meningothelial cell proliferation. The morphology and immunohistochemical profile of the spindle cells were different from those of conventional meningothelial cells. The meningothelial cells showed a typical immunoreactivity of conventional meningiomas, while the spindle cells displayed a strong expression of vimentin. The Ki-67 labelling index was uniformly low in all cases, and none of cases expressed p53 protein. In summary, the recognition of meningothelial cells in massively sclerotic lesions is helpful for a correct diagnosis. In the cases with a total absence of meningothelial cells, however, the vague collagenous whorls are more diagnostic rather than immunohistochemistry. Considering association with clear cell meningioma, prospective and retrospective long-term follow-up is necessary for deciding whether reminiscent clear cell meningiomas should be separated from sclerosing meningioma or not.     

Proliferation and Dna fragmentation in meningioma subtypes

H. Maier, J. Wanschitz, R. Sedivy, K. Rössler, D. Öfner and H. Budka (1997) Neuropathology and Applied Neurobiology 23, 496–506 Proliferation and DNA fragmentation in meningioma subtypes Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas. To substantiate this three-step scale of malignancy, we assessed the proliferative activity reflected by Ki-67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas. The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL-2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas. Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas. MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P 0.0001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas. IST indices rose with increasing malignancy and correlated with MIB1 LI (P 0.0001); they showed a weak inverse correlation with BCL-2 immunoexpression (P= 0.05). BCL-2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis. Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale, (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas.     

Ossified thoracic spinal meningioma in childhood: A case report and review of the literature

Spinal ossified meningiomas are extremely rare. This is a report of a study on a 15-year-old boy with thoracic spinal ossified meningioma. The meningioma was resected totally. Histopathological examination revealed a transitional meningioma (psammomatous+meningothelial). Immunohistochemically, Ki 67 antibody was applied but no positive staining was present. The surgical and pathological aspects of spinal ossified meningiomas were reviewed.     

Investigation of blood flow in meningothelial and fibrous meningiomas by xenon-enhanced CT scanning

We investigated whether xenon-enhanced computed tomography was able to separate meningothelial meningioma from fibrous meningioma. Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (< 32 mm) and there was little or no peritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow and the contralateral tissue blood flow were determined. The ratio of these parameters was 1.753 +/- 0.467 for meningothelial meningiomas and 0.809 +/- 0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. In conclusion, xenon-enhanced computed tomography showed a difference between smaller meningothelial and fibrous meningiomas in patients with normal surrounding brain tissue. We could not confirm that xenon-enhanced computed tomography was able to distinguish the subtype of meningioma because of the small number of subjects in this study, but our findings might expand interest in the clinical use of this method.     

Expression of c-Myc, neurofibromatosis Type 2, somatostatin receptor 2 and erb-B2 in human meningiomas: relation to grades or histotypes

Meningiomas, which originate from arachnoid cells, represent one of the largest subgroups of intracranial tumors. They are generally benign, but can progress to malignancy. The aim of our study was to determine the expression of 4 genes, c-Myc, neurofibromatosis Type 2 (NF2), somatostatin receptor isoform 2 (sst2) and erb-B2, that have been associated with tumorogenesis or, possibly, with aggressive behavior or recurrence of meningiomas. We measured levels of mRNAs coding for these genes by qRT-PCR in 51 cases and levels ofc-Myc protooncogene and sst2 protein by immunohistochemistry in 26 cases of meningiomas of various grades and histotypes. C-Myc mRNA and protein levels were not grade-related, but validated subdivision of the 36 benign meningiomas into two groups, Groups IA and IB, based on histological and clinical features (Ki-67-proliferative index, absence or presence of mitoses, rate of recurrence and incidence of perilesional edema). In addition to histopathological grading, c-Myc expression may be useful in predicting tumor recurrence in patients with low-grade meningiomas. NF2 mRNA levels and sst2 mRNA and receptor levels were not grade-related, but were histotype-related, with significantly higher levels in the meningothelial subtype than in the fibroblastic subtype. Erb-B2 mRNA levels were not grade- or histotype-related. Furthermore, the high expression of sst2 in meningothelial meningioma suggests the possibility of a different tumorigenesis process in this meningioma subtype and may open perspectives for the diagnosis and therapy of this subtype using somatostatin as an antiproliferative agent.     

Cytoplasmic iron deposition is associated with the expression of oxidative DNA damage marker in meningiomas

Angiomatous meningiomas are rare meningioma subtypes, which are characterized by abundant, well‐formed vessels. We encountered two cases of newly diagnosed angiomatous meningiomas exhibiting tumor cells with brown pigments, which were histochemically proven to be iron. In an attempt to understand its pathological significance, we assessed this unusual finding in representatives for each grade of meningiomas and immunoexpression of transferrin receptor (CD71) and the oxidative DNA damage marker, 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). Iron deposition in the tumor cells was observed in 8/15 (53%) angiomatous meningioma cases, 2/6 (33%) microcystic meningiomas and 2/20 (10%) meningothelial meningiomas, which included clustered microvessels, but not in fibrous, atypical or anaplastic meningiomas (P = 0.001). Cytoplasmic CD71 expression was largely negative in angiomatous meningioma cases, but positive in meningothelial and high‐grade meningiomas, suggesting that the transferrin‐dependent iron transporter was involved in iron uptake in meningiomas. Nuclear expression of 8‐OHdG was observed in ≥50% of the tumor cells in all 15 cases of angiomatous meningioma and was associated with the presence of regressive histopathological findings, such as hyalinized vessels and cystic changes. In addition, the fraction of iron‐containing tumor cells was correlated to those expressing 8‐OHdG (P = 0.005). Our finding indicates that cytoplasmic iron deposition in tumor cells is characteristic of highly vascularized benign meningiomas and related to increased oxidative DNA damage markers.     

Recurrent and atypical meningiomas--a multiparametric study using Ki67 labelling index,AgNOR and DNA Feulgen staining

OBJECTIVE: Histological analysis has limited value to predict the biological behavior of meningiomas. In this study, we investigated the utility of indicators of cell proliferation in the evaluation of histologically benign meningiomas. MATERIALS AND METHODS: For this purpose, 50 meningothelial meningiomas, 50 atypical meningiomas and 8 primary benign meningiomas with their recurrences were studied. For each case the Ki67 labeling index (LI), DNA ploidy and AgNOR were evaluated and the results quantitatively processed and assessed by computerized image analyzer. RESULTS: The Ki67 labelling showed a low index (11.3%) in typical meningiomas and primary meningiomas (13.6%). In contrast, it was higher in atypical (26.6%) and recurrent meningiomas (28%). Similar results were obtained for the AgNOR granule count which showed that typical and primary meningiomas had mean 1.51 - 1.49, whereas recurring meningiomas and atypical meningiomas had mean values of 1.92 and 1.98, respectively. DNA ploidy revealed in the hyperpolyploid region between 4c - 16c: 7.02% of the nuclei in primary meningiomas, 17.98% of the nuclei in recurring meningiomas and 24.63% of the nuclei in atypical meningiomas. CONCLUSION: Our results suggest that evaluation of cell proliferation using Ki67 LI, DNA ploidy and AgNOr, integrated with standard histopathology, can provide better information for a correct grading of meningiomas.     

Investigation of blood flow in meningothelial and fibrous meningiomas by xenon-enhanced CT scanning

Abstract

We investigated whether xenon-enhanced computed tomography was able to separate meningothelial meningioma from fibrous meningioma. Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (<32mm) and there was little or no péritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow and the contralateral tissue blood flow were determined. The ratio of these parameters was 7.753 ± 0.467 for meningothelial meningiomas and 0.809±0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. In conclusion, xenon-enhanced computed tomography showed a difference between smaller meningothelial and fibrous meningiomas in patients with normal surrounding brain tissue. We could not confirm that xenon-enhanced computed tomography was able to distinguish the subtype of meningioma because of the small number of subjects in this study, but our findings might expand interest in the clinical use of this method. [Neurol Res 2000; 22: 615-619]     

Analysis of the PTEN gene in human meningiomas

N. Peters, R. Wellenreuther, B. Rollbrocker, Y. Hayashi, B. Meyer-Puttlitz, E-M. Duerr, D. Lenartz, D.J. Marsh, J. Schramm, O.D. Wiestler, R. Parsons, C. Eng & A. von Deimling (1998) Neuropathology and Applied Neurobiology 24, 3–8
Analysis of the PTEN gene in human meningiomas
Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2) plays an important role in the pathogenesis of the transitional, fibroblastic and malignant variants of human meningiomas. No specific genes have been associated with the pathogenesis of meningothelial meningiomas and with the progression to anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and 14q have been implicated in the process of malignant progression. Recently, PTEN (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF—regulated and epithelial cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3. Initial studies revealed mutations of PTEN in limited series of glioblastomas, breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I), 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of the anaplastic meningiomas carried a somatic mutation. In addition, all tumours were examined for the presence of homozygous deletions of PTEN but these were not detected in any of the meningiomas. Our data suggest that mutations in PTEN are not involved in the formation of low grade meningiomas, but may contribute to malignant progression in a fraction of anaplastic meningiomas.     

NF2 gene expression in sporadic meningiomas: Relation to grades or histotypes real time‐PCR study

One of the most common regions involved in the meningiomas tumorigenesis is chromosome 22q where the NF2 gene resides. The deficiency or loss of the NF2 gene product, merlin/schwannomin, plays a role in tumor development and metastatization. Conflicting results have been reported on the prognostic value of merlin in meningiomas. Several studies have indicated NF2 gene inactivation as an early tumorigenic event unrelated to the histological grade or clinical behavior. On the contrary, the NF2 gene alteration rate differs between the different histotypes. A pathogenesis independent from the NF2 gene has been suggested in meningothelial meningiomas. In the present work, we studied the NF2 gene expression through real time‐PCR (RT‐PCR) in 30 meningiomas. The average of the NF2 gene expression of all meningiomas was considered as reference value. The average of expression of WHO grade I and II meningiomas was higher than the average of all meningiomas, whereas that of WHO grade III meningiomas was lower. When we compared the NF2 gene expression in the different meningioma grades we did not note a significant difference (P = 0.698) despite the tendency to decrease from grade I to grade III. The average expression of meningothelial meningiomas was higher than the reference value, and that of non‐meningothelial meningiomas was lower. The difference in NF2 gene expression between meningothelial and non‐meningothelial meningiomas was statistically significant (P = 0.013). Our data supports the finding that alterations in NF2 gene alteration are histotype related but not grade related.     

Neurotensin receptors in human meningiomas.

We have investigated the presence of neurotensin receptors in human meningiomas by in vitro binding autoradiography. Ten of the 12 meningiomas tested displayed specific [3H]neurotensin binding. All meningothelial (n = 3) and transitional (n = 5) meningiomas were positive, whereas only 2 of the 4 fibroblastic meningiomas showed measurable concentrations of neurotensin binding sites. Within the tumors, [3H]neurotensin binding was preferentially observed in syncytial areas. Saturation experiments showed that the maximal binding capacity (Bmax) greatly varied among tumors, ranging from low values to more than 290 fmol/mg of protein. All positive tumors had neurotensin binding sites with a dissociation constant (kd) within the nanomolar range and a pharmacological specificity for [3H]neurotensin similar to neurotensin receptors.     

Lectin histochemistry in the aged dog brain

Formalin-fixed and paraffin-embedded canine brains were examined histochemically using 15 selected lectins. Concanavalin A (Con A), Lens culinaris agglutinin, Lycopersicon esculentum agglutinin (LEL) and Limulus polyphemus agglutinin (LPA) labeled neurons in an age-dependent manner. These and some other lectins [Dolichos biflorus agglutinin (DBA), Vicia villosa agglutinin (VVA), Ricinus communis agglutinin 120 (RCA-I), Bandeiraea simplicifolia agglutinin (BSL-I), and Phaseolus vulagaris agglutinin-L (PHA-L)] also age-dependently labeled glial cells. These results indicate that monosaccharide composition and biochemical metabolism in brain cells change with age and that these lectins may be useful as histochemical markers for investigating senile changes in the canine brain. However, no significant correlation was found between ApopTag-positive and lectin-positive cells. Amyloid plaques were positive for Con A, DBA, Glycine maximus agglutinin (SBA), LEL, PHA-L, Limax flavus agglutinin (LFA) and VVA. Among these lectins, VVA, SBA and LFA intensely stained amyloid both in blood vessel walls and senile plaque cores. Therefore, the sugar residues recognized by these lectins likely play specific roles in β-amyloid deposition in the aged dog brain. Received: 2 June 1997 / Revised: 21 July 1997, 28 August 1997 / Accepted: 3 October 1997