[Contribution of temozolomide chemotherapy for intramedullary grade II spinal cord astrocytomas in adults: Our experience]. / Place de la chimiothérapie de type témozolomide pour les astrocytomes intramédullaires de grade II de l'adulte : notre expérience.

INTRODUCTION: Grade II intramedullary astrocytomas are rare tumors. Despite a well-defined role of adjuvant temozolomide chemotherapy for brain gliomas, the contribution of this therapy for intramedullary gliomas is not yet clearly defined. METHOD: We retrospectively analyzed the data of 5 adult patients treated with temozolomide between 2008 and 2015 for a grade II intramedullary astrocytoma with progression after surgery. RESULTS: Five patients from 19 to 70 years of age (median, 37years) underwent a second surgery for the progression of a grade II intramedullary astrocytoma (median progression-free survival 26months [8-90]). All tumors remained grade II. Due to a second clinical or/and radiological tumor progression, the patients were treated with temozolomide after a 37months median progression-free survival (5-66). All patients received at minimum 12 cycles (mean 14 ± 5; range 12-24) of temozolomide (150-200mg/m2/day, 5days/28days). All patients were alive after a 10-year median follow-up after diagnosis (6-13). All patients were able to walk except one, who was previously in McCormick autonomy grade IV before chemotherapy. The McCormick autonomy rating after temozolomide was stable for 4 patients and improved for 1 patient. The treatment was delayed once for hematological toxicity. CONCLUSION: Temozolomide stabilized all 5 patients without any major toxicity. Based on this experience that needs to be confirmed, we consider that temozolomide should be envisaged within the therapeutic arsenal for progressive intramedullary grade II astrocytomas.

[Supraorbital approach to treat a fronto-orbital fracture with pneumocephaly, a minimal invasive technique]. / Abord supraorbitaire pour traiter une fracture frontale avec pneumocéphalie, une technique peu invasive.

We describe a supraorbital approach through an upper eyebrow skin incision to treat a fronto-orbital fracture with pneumocephaly in a 84-year-old cardiac patient. The clinical and cosmetic results are excellent. This case is illustrated by pre- and postoperative CT-scan and MRI as well as pictures showing the minimal invasive technique.

Why dapsone stops seizures and may stop neutrophils' delivery of VEGF to glioblastoma.

Lopez-Gomez et al. recently published remarkable but mechanistically unexplained empirical evidence that the old antibiotic dapsone has antiepileptic activity. We addressed the question "Why should a sulfone antibiotic reduce seizures?". We report here our conclusions based on data from past studies that seizures are associated with elevated interleukin-8 (IL-8) and that dapsone inhibits IL-8 release and function in several different clinical and experimental contexts. Diverse CNS insults cause an increase in CNS IL-8. Thus, the pro-inflammatory environment generated by increase IL-8 leads to a lower seizure threshold. Together this evidence indicates dapsone exerts anti-seizure activity by diminishing IL-8 signalling. Since IL-8 is clearly upregulated in glioblastoma and contributes to the florid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function.

Phenazines and cancer.

Phenazines are a large group of natural and synthesised nitrogen-containing heterocycles, including more than 100 different compounds of natural origin and over 6000 synthetic compounds. Many of these compounds have been investigated as potential anti-cancer agents. Despite a large number of research publications, no recent attempt to summarise and critically evaluate the experimental findings relating to the anti-cancer activity of this class of compounds has been made. The present review fills this gap in the literature and discusses both natural and synthetic phenazines with a critical focus on in vitro, in vivo and available clinical anti-cancer activities of these compounds.

[What should be done in the event of incidental meningioma?]. / Que faire en cas de découverte fortuite d'un méningiome?

BACKGROUND AND PURPOSE: The growing use of magnetic resonance and computed tomography imaging has facilitated the diagnosis of brain tumours even before the presence of clinical signs. A significant proportion of incidental lesions identified will be meningiomas, i.e. more than 40% of the diagnosed meningiomas are not associated with clinical signs. The natural history of incidental asymptomatic intracranial meningiomas must be known to develop the optimal therapeutic strategy: what is the tumor growth rate? How many asymptomatic tumours eventually become symptomatic? METHOD: The literature was reviewed in an attempt to answer these questions. RESULTS: In cases of incidental meningioma, its location, size and radiological aspect, the patient's age, the eventual unknown symptoms and the multiplicity of the lesions must all be considered. The radiological characteristics associated with low tumoral growth rate are the existence of calcifications and hypointense regions on T2-weighted MR images. On the radiological aspect, more than 60% of asymptomatic meningiomas will not grow in size. However, some meningiomas, even small in size, must be treated because of their location or the risk of producing neurological deficits. CONCLUSION: We recommend neurosurgical consultation for all patients with an incidental meningioma.

[Glioblastoma treatment in 2010]. / Traitement des glioblastomes à l'aube de 2010.

The treatment of glioblastomas requires a multidisciplinary approach because despite the progresses in surgical and iconographic managements associated with research knowledge this disease presently remains incurable and progresses during the 6 months after its diagnose. Current recommendations are that patients with glioblastoma should undergo maximum surgical resection followed by concurrent radiation and chemotherapy with the alkylating drug temozolomide, followed subsequently by additional adjuvant temozolomide for a period of up to 6 months. Temozolomide mechanism of action is complex and we have recently evidenced a temozolomide-associated anti-angiogenic activity in vitro and in vivo on preclinical human glioblastoma models. We describe in the current review the temozolomide-associated antiangiogenic activity. We also describe here the major signaling pathways that can be constitutively activated in migrating glioma cells, and which render these cells resistant to proapoptotic insults such as conventional chemotherapies. In light of this resistance, we therefore describe the targeted therapies and local drug delivery systems which could be used to complement conventional treatments. We have reviewed more than 400 ongoing clinical trials with respect to these new targeted therapy approaches alone or in combination for glioblastoma therapy and we also emphasize the importance of vaccinotherapy. We conclude our review with a therapeutic model that could be used in the light of the present knowledge.

Present and potential future adjuvant issues in high-grade astrocytic glioma treatment.

Despite major advances in the management of malignant gliomas of which glioblastomas represent the ultimate grade of malignancy, they remain characterized by dismal prognoses. Glioblastoma patients have a median survival expectancy of only 14 months on the current standard treatment of surgical resection to the extent feasible, followed by adjuvant radiotherapy plus temozolomide, given concomitantly with and after radiotherapy. Malignant gliomas are associated with such dismal prognoses because glioma cells can actively migrate through the narrow extra-cellular spaces in the brain, often travelling relatively long distances, making them elusive targets for effective surgical management. Clinical and experimental data have demonstrated that invasive malignant glioma cells show a decrease in their proliferation rates and a relative resistance to apoptosis (type I programmed cell death) as compared to the highly cellular centre of the tumor, and this may contribute to their resistance to conventional pro-apoptotic chemotherapy and radiotherapy. Resistance to apoptosis results from changes at the genomic, transcriptional and post-transcriptional level of proteins, protein kinases and their transcriptional factor effectors. The PTEN/ PI3K/Akt/mTOR/NF-kappaB and the Ras/Raf/MEK/ERK signaling cascades play critical roles in the regulation of gene expression and prevention of apoptosis. Components of these pathways are mutated or aberrantly expressed in human cancer, notably glioblastomas. Monoclonal antibodies and low molecular-weight kinase inhibitors of these pathways are the most common classes of agents in targeted cancer treatment. However, most clinical trials of these agents as monotherapies have failed to demonstrate survival benefit. Despite resistance to apoptosis being closely linked to tumorigenesis, tumor cells can still be induced to die by non-apoptotic mechanisms such as necrosis, senescence, autophagy (type II programmed cell death) and mitotic catastrophe. Temozolomide brings significant therapeutic benefits in glioblastoma treatment. Part of temozolomide cytotoxic activity is exerted through pro-autophagic processes and also through the induction of late apoptosis. Autophagy, type II programmed cell death, represents an alternative mechanism to overcome, at least partly, the dramatic resistance of many cancers to pro-apoptotic-related therapies. Another way to potentially overcome apoptosis resistance is to decrease the migration of malignant glioma cells in the brain, which then should restore a level of sensitivity to pro-apoptotic drugs. Recent series of studies have supported the concept that malignant gliomas might be seen as an orchestration of cross-talks between cancer cells, microenvironment, vasculature and cancer stem cells. The present chapter focuses on (i) the major signaling pathways making glioblastomas resistant to apoptosis, (ii) the signaling pathways distinctly activated by pro-autophagic drugs as compared to pro-apoptotic ones, (iii) autophagic cell death as an alternative to combat malignant gliomas, (iv) the major scientific data already obtained by researchers to prove that temozolomide is actually a pro-autophagic and pro-apoptotic drug, (v) the molecular and cellular therapies and local drug delivery which could be used to complement conventional treatments, and a review of some of the currently ongoing clinical trials, (vi) the fact that reducing the levels of malignant glioma cell motility can restore pro-apoptotic drug sensitivity, (vii) the observation that inhibiting the sodium pump activity reduces both glioma cell proliferation and migration, (viii) the brain tumor stem cells as a target to complement conventional treatment.

[Intramedullary cavernomas: personal series of 24 cases]. / Les cavernomes intramédullaires: série personnelle de 24 cas.

Intramedullary cavernomas are rare, but with routinely use of MRI detection has improved, raising the problem of choosing the adequate management approach: conservative or surgical. Cavernomas are vascular malformations, but, as hemangioblastomas they appear as vascular tumors of the spinal cord. They can be durably asymptomatic. The symptoms are a progressive clinical deterioration or acute spinal dysfunction (tetra or paraplegia) in case of hemorrhage. Cavernomas have a typical aspect with MRI in contrast with intramedullary gliomas. The lesion is often superficial, covered by the pia-mater, visible immediately after opening the dura, the approach is direct; but in few cases the cavernoma is deep seated in the spinal cord and not visible, the approach is through the midline. It is recommended to perform a complete "en bloc" resection. A yearly MRI control is necessary to search possible "de novo" cases.

[Glioblastomas are resistant to apoptosis but less resistant to the autophagic process]. / Les glioblastomes sont résistants a l'apoptose mais de façon moindre au processus d'autophagie.

Malignant gliomas of which glioblastomas represent the ultimate grade of malignancy are characterized by dismal prognoses because malignant glioma cells present both important proliferation and neoangiogenesis processes and can actively migrate through the narrow extra-cellular spaces in the brain, often travelling relatively long distances, making them elusive targets for effective surgical management. Invasive malignant glioma cells show a decrease in their proliferation rates and a relative resistance to apoptosis (type I programmed cell death) but seem less resistant to autophagic cell death (type II programmed cell death). Autophagic cell death represents an alternative mechanism to overcome, at least partly, the dramatic resistance of glioblastomas to pro-apoptotic-related therapies. Another way to potentially overcome apoptosis resistance is to decrease the migration of malignant glioma cells in the brain, which then should restore a level of sensitivity to pro-apoptotic drugs. We conclude this work with an algorithm showing the optimal current treatment for glioblastoma with the potent future innovations.

Endovascular treatment of intracranial aneurysms with a branch arising from the sac.

BACKGROUND AND PURPOSE: The endovascular treatment (EVT) of intracranial aneurysms is no more limited by the presence of a branch at the neck or by the neck width. Saccular aneurysms with a branch arising from the sac, however, are mostly candidates for surgery rather than embolization. We prospectively evaluated the feasibility and safety of the EVT in such cases. METHODS: Between May and November 2004, 9 consecutive patients with a saccular aneurysm that presents a branch arising from the sac were treated by embolization. There were 7 women and 2 men (mean age, 58 years). Six patients presented with a subarachnoid hemorrhage (SAH), and 3 were asymptomatic. All patients were treated by selective coiling with (n = 6) or without (n = 3) the remodeling technique. Clinical outcome was assessed with a modified Glasgow Outcome Scale at 3 months. RESULTS: EVT was successfully performed in all patients and resulted in 7 excellent outcomes and 2 deaths related to SAH complications. The arterial branch could be preserved in 7 cases and intentionally occluded in 2. Neither embolic nor ischemic complication occurred in the vascular territory of the involved branch. Angiographic results showed 5 neck remnants, 2 incomplete occlusions, and 2 complete occlusions. No rebleeding occurred. CONCLUSION: Our study, though limited by its small patient population, suggests that saccular intracranial aneurysms with a branch arising from the sac may be treated by endovascular approach with excellent clinical results; however, larger series with long-term follow-up are mandatory to confirm these preliminary results mostly in terms of anatomic stability.

Cathepsin B, D and K expression in adamantinomatous craniopharyngiomas relates to their levels of differentiation as determined by the patterns of retinoic acid receptor expression.

AIMS: To investigate the potential predictive value of cathepsins B, D and K in a series of 51 adamantinomatous craniopharyngiomas. While almost always benign, craniopharyngiomas exhibit a high propensity to recur postsurgically and biological markers are therefore needed to predict their recurrence. We have previously demonstrated the potential predictive value of retinoic acid receptors (RARs) (Lefranc et al., J. Neurosurg. 2003; 98; 145-153). METHODS AND RESULTS: Computer-assisted microscopy was used to determine quantitatively the immunohistochemical levels of expression of the alpha, beta and gamma RAR subtypes and cathepsins B, D and K. The levels of expression of cathepsin D and of cathepsin B correlated significantly with the levels of expression of RARbeta. The levels of expression of cathepsin K correlated significantly with the levels of expression of RARgamma. CONCLUSIONS: Recurrent adamantinomatous craniopharyngiomas are characterized by low levels of RARbeta and high levels of RARgamma. The tendency to recurrence seems, at least partly, to relate to the fact that (i) craniopharyngiomas with low levels of RARbeta express low levels of cathepsin D, and (ii) craniopharyngiomas with high levels of RARgamma express high levels of cathepsin K.

Differential expression of S100 calcium-binding proteins in epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas.

AIMS: To investigate whether epidermoid cysts, branchial cysts, craniopharyngiomas and cholesteatomas express S100 proteins differentially by immunohistochemical assaying the presence of S100A1, S100A2, S100A3, S100A4, S100A5, S100A6 and S100B. METHODS AND RESULTS: Immunopositivity/negativity was recorded for each S100 protein in a series of 52 cases consisting of 12 epidermoid cysts, 12 branchial cysts, 15 adamantinomatous craniopharyngiomas and 13 acquired cholesteatomas. Except in the case of the craniopharyngiomas, immunoreactivity was assessed independently in the basal membrane and the basal, the internal and the keratin layers. Our data show that in contrast to S100B, which was rarely expressed, S100A1, S100A2, S100A4 and S100A5 were often present in these four types of epithelial lesions. S100A3 and S100A6 and, to a lesser extent, S100A5 were the most differentially expressed proteins across the different histopathological groups analysed. These three proteins are expressed more often in craniopharyngiomas and cholesteatomas, the two more aggressive types of lesions. CONCLUSIONS: This is the first study to report data on the expression of seven S100 proteins in different histopathological groups of epithelial head and neck lesions, whose precise embryological origins are still a matter of debate. S100 proteins could possibly be used as markers to target this embryonic origin, since our results show that S100A3 and S100A6 (and, to a lesser extent, S100A5) are expressed differentially across these different groups of epithelial lesions.

[The neurosurgery department]. / Le Service de Neurochirurgie.

Opened on November 1st, 2001, the Department of Neurosurgery has progressively grown to become worldwide renown in a few years. All the pathologies are covered, from lumbar disc hernia to intracranial tumors and vascular malformations. But the originality stays into the exceptional environment by the concentration of logistic resources and the ability of clinician and researchers who daily collaborate with the neurosurgical team. The Department of Neurosurgery has a strong reputation in several fields like intraspinal cord tumors or Pet-guided Neurosurgery in stereotactic biopsies, neuronavigation and Gamma Knife and, generally speaking, in the original approach of the treatment and follow-up of brain tumors. Neurodegenerative diseases also benefit of modern approaches trough the Gamma Knife, deep brain stimulation or fetal cell grafting into the brain in Parkinson and soon in Huntington diseases. Last but not least, the arrival for the 25th anniversary of Erasme Hospital of an interventional MRI will allow to follow in real-time the resection of brain tumors with an obvious benefit for the surgical performances and the quality of life of the patients. It will also open a new window for neurosurgical research through combination with functional MRI and Pet-Scan, reinforcing the reputation of Erasme Neurosurgical Department who has been distinguished in 1997 by the World Health Organisation as "WHO Collaborating Center for Research and Training in Neurosurgery" and nominated again in 2002 for a new 4-year period, which is unique in the Neurosurgical World.

Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features.

Glioma cell attachments to substratum play crucial roles in the invasion by glioma cells of normal brain tissue. These attachments are mediated through interactions between extracellular matrix (ECM) components, integrins, focal adhesion-linked molecules, and the actin cytoskeleton. In the present study, we investigate the molecular elements involved in cell substratum attachments in human glial tumors and their potential relationships to prognostic features. We used 10 human glioma cell lines, for which we characterized glial differentiation by means of quantitative RT-PCR for nestin, vimentin, and GFAP mRNA. We quantitatively determined the amounts of laminin, fibronectin, vitronectin, and thrombospondin secreted by these glioma cell lines in vitro, as well as the amount of each of the eight beta integrin subunits and the adhesion complex-related molecules, including talin, vinculin, profilin, zyxin, alpha-actinin, paxillin, and VASP. After quantification of the levels of migration and invasion of these 10 cell lines in vitro and, through grafts into the brains of nude mice, of their biological aggressiveness in vivo, it appeared that the levels of the beta 5 integrin subunit and alpha-actinin were directly related to biological aggressiveness. These experimental data were clinically confirmed because increasing immunohistochemical amounts of the beta 5 integrin subunit and alpha-actinin were directly related to dismal prognoses in the case of astrocytic tumors. In addition, we show that the beta 4 integrin subunit are expressed significantly more in oligodendrogliomas than in astrocytic tumors. A potential role for the beta 8 integrin subunit in glioma cell substratum attachments is also emphasized.

Intracranial meningiomas revealed by non-traumatic subdural haematomas: a series of four cases.

OBJECTIVE: A review of the literature shows 33 cases of ipsilateral subdural haematomas (SDH) associated with meningiomas. We suggest that physiopathological mechanisms could be primary haemorrhages from abnormal vessels in the tumours and the opening of the intratumoral haematomas into the subdural space. Our working hypothesis relies on a series of 300 meningiomas operated upon in our department since 1990; of these, 4 were revealed by SDH. CLINICAL PRESENTATION: The four patients surgically treated in our department had developed a progressive impairment of consciousness. There was no history of trauma, blood dyscrasia or anticoagulant therapy. After diagnosis, the SDH was drained, and the meningeal tumour was totally resected once it had been discovered. In one case, the presence of a tumour was demonstrated by magnetic resonance imaging (MRI) performed only after the evacuation of a recurrent SDH. INTERVENTION: In each case, an acute SDH showing signs of recent bleeding was evacuated. The meningeal tumour discovered proved to be the source of the haemorrhage because of the numerous fresh blood clots both around and inside it. HISTOLOGY: In the four cases histology showed fresh intratumoral haemorrhages (ITH), large blood vessels with thin endothelial linings and haemosiderin deposits. In this review, SDH is associated with other haemorrhage sites in 24 of 37 cases (33+our 4 cases). ITH was present in 14 cases (40%). CONCLUSION: The treatment should consist of the extirpation of the meningioma at the same time as the evacuation of the haematoma. If primary ITH from abnormal vessels is the source of SDH, complete meningioma resection should prevent the recurrence of SDH. Subdural membranes and haematomas should therefore be inspected for their intrinsic pathology, especially when there is no history of trauma.

Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma.

Protein (lectin)-carbohydrate interaction is supposed to be relevant for tumor cell behavior. The aims of the present work are to investigate whether galectin-1 modulates migration/invasion features in human gliomas in vitro, whether it can be detected in human gliomas immunohistochemically, and whether its expression is attributable to certain glioma subgroups with respect to invasion and prognosis. For this purpose, we quantitatively determined (by computer-assisted microscopy) the immunohistochemical expression of galectin-1 in 220 gliomas, including 151 astrocytic, 38 oligodendroglial, and 31 ependymal tumors obtained from surgical resection. We also xenografted three human glioblastoma cell lines (the H4, U87, and U373 models) into the brains of nude mice in order to characterize the in vivo galectin-1 expression pattern in relation to tumor invasion of the normal brain parenchyma. In addition, we characterized the role in vitro of galectin-1 in U373 tumor astrocyte migration and kinetics. Our data reveal expression of galectin-1 in all human glioma types with no striking differences between astrocytic, oligodendroglial, and ependymal tumors. The level of galectin-1 expression correlated with the grade in the group of astrocytic tumors only. Furthermore, immunopositivity of high-grade astrocytic tumors from patients with short-term survival periods was stronger than that of tumors from patients with long-term survivals. In human glioblastoma xenografts, galectin-1 was preferentially expressed in the more invasive parts of these xenografts. In vitro experiments revealed that galectin-1 stimulates migration of U373 astrocytes.

Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration.

Galectins, a family of mammalian lectins with specificity to beta-galactosides, are involved in growth-regulatory mechanisms and cell adhesion. A relationship is assumed to exist between the levels of expression of galectins and the level of malignancy in human gliomas. A comparative study of this aspect in the same series of clinical samples is required to prove this hypothesis. Using computer-assisted microscopy, we quantitatively characterized by immunohistochemistry the levels of expression of galectins-1, -3 and -8 in 116 human astrocytic tumors of grades I to IV. Extent of transcription of galectins-1, -3, and -8 genes was investigated in 8 human glioblastoma cell lines by means of RT-PCR techniques. Three of these cell lines were grafted into the brains of nude mice in order to characterize in vivo the galectins-1, -3 and -8 expression in relation to the patterns of the tumor invasion of the brain. The role of galectin-1, -3 and -8 in tumor astrocyte migration was quantitatively determined in vitro by means of computer-assisted phase-contrast videomicroscopy. The data indicate that the levels of galectin-1 and galectin-3 expression significantly change during the progression of malignancy in human astrocytic tumors, while that of galectin-8 remains unchanged. These three galectins are involved in tumor astrocyte invasion of the brain parenchyma since their levels of expression are higher in the invasive parts of xenografted glioblastomas than in their less invasive parts. Galectin-3, galectin-1, and to a lesser extent galectin-8, markedly stimulate glioblastoma cell migration in vitro. Since bands for the transcripts of human galectins-2, -4 and -9 were apparently less frequent and intense in the 8 human glioblastoma cell lines, this system provides an excellent model to assign defined roles to individual galectins and delineate overlapping and distinct functional aspects.

[Cerebellar hemorrhage complicating a supratentorial craniotomy. A case report and review of the literature]. / Hémorragie cérébelleuse compliquant une crâniotomie supratentorielle. Un cas rapporté et revue de la littérature.

Postoperative cerebellar hemorrhage after a supratentorial craniotomy represents a rare event. We report a case of a patient with a meningioma of the jugum who developed suddenly after surgery a neurological deterioration due to a cerebellar hemorrhage detected on the CT scan. An occipital craniectomy and an external ventricular drainage were performed in emergency. A complete neurological recovery was observed after surgery. Nineteen similar other cases are found in the literature. Pre- and postoperative high blood pressure, lowered intracranial pressure and mispositioning of the head during surgery could be at the origin of the hemorrhage. Size of the hemorrhage, time between diagnosis and treatment represent two prognostic factors. All patients, who present a neurological deterioration in postoperative course, must have CT scan including posterior fossa.

Differential expression of S100 calcium-binding proteins characterizes distinct clinical entities in both WHO grade II and III astrocytic tumours.

The computer-assisted microscopic analysis of Feulgen-stained nuclei enabled us to identify two subgroups of astrocytomas (WHO grade II) and two subgroups of anaplastic astrocytomas (WHO grade III) with significantly distinct clinical outcomes (Decaestecker et al. Brain Pathol 1998; 8: 29-38). The astrocytomas labelled in the present study as typical (TYP-ASTs) behaved clinically like real astrocytomas while atypical astrocytomas (ATYP-ASTs) behaved similarly to anaplastic astrocytomas. The anaplastic astrocytomas that we labelled as typical (TYP-ANAs) behaved clinically like anaplastic astrocytomas while atypical ones (ATYP-ANAs) behaved like glioblastomas. In the present study, we investigate whether some biological characteristics could be evidenced across these four groups of TYP- and ATYP-ASTs and TYP- and ATYP-ANAs. The data show that the levels of expression (immunohistochemically assayed and quantitatively determined by means of computer-assisted microscopy) of vimentin, the glial fibrillary acidic protein and the platelet-derived growth factor-alpha did not differ significantly across these four groups of astrocytic tumours. The level of cell proliferation (determined by means of both the anti-proliferating cell nuclear antigen and the anti-MIB-1 antibodies; P < 0.001 to P < 0.0001) differed very significantly between the astrocytomas and anaplastic astrocytomas, but not between the typical and atypical variants identified in each group. In sharp contrast, the levels of expression of the S100A3 and S100A5 proteins differed markedly in the solid tumour tissue in relation to the astrocytic tumour types and grades. In addition, while the levels of expression of S100A6 did not change in the astrocytic tumour tissue in relation to histopathological grade, the levels of expression of this S100 protein (but not those of S100A3 and S100A5) differed markedly in the blood vessel walls according to whether these vessels originated from low- or high-grade astrocytic tumours.