Different expression of adhesion molecules on stromal cells and endothelial cells of capillary hemangioblastoma

Cell-cell and cell-matrix interactions are essential for many basic functions, including differentiation and development. In pathological conditions such as inflammation and tumorigenesis adhesive events also play a major role. Cellular adhesion is mediated by specific molecules expressed by both normal and neoplastic tissues. Capillary hemangioblastoma is a tumor of controversial origin, characterized by two major components, vacuolated stromal cells and a capillary network. In order to shed light on the differentiation of the stromal cells and the interactions between the two major components of hemangioblastoma we studied the expression of several adhesion molecules by immunocytochemistry. The endothelium-associated adhesion molecules (ICAM-1, ICAM-2, VCAM-1, PECAM-1 and ELAM-1) were expressed by endothelial cells within the tumors, but not by stromal cells. In contrast, the stromal cells showed strong neuronal cell adhesion molecule (NCAM/CD56) expression, further distinguishing them from endothelial cells. In addition, the stromal cells expressed CD44, which is of interest, as this membrane protein is linked to ezrin, a cytoskeleton-associated protein also expressed by stromal cells. We conclude that the stromal cells and endothelial cells of capillary hemangioblastoma exhibit quite divergent expression patterns of adhesion molecules. The NCAM expression in stromal cells suggests neuroectodermal or mesenchymal differentiation of this tumor. In addition, the NCAM expression could contribute to the sometimes problematic differential diagnosis between capillary hemangioblastoma and metastatic renal cell carcinoma of the central nervous system. Received: 17 December 1995 / Revised, accepted: 13 May 1996     

Computed tomography and angiography do not reliably discriminate malignant meningiomas from benign ones

Summary Histological anaplasia, found in up to 10% of meningiomas, is an important prognostic sign as it is associated with increased recurrence rate and volume growth rate. We studied in retrospect a series of 230 primary intracranial meningiomas to discover whether histological anaplasia can be reliably foreseen in CT scans and angiograms. 205 meningiomas were histologically benign, and 25 meningiomas were classified as malignant (atypical or anaplastic), with either incipient (20) or overt (5) signs of anaplasia. Often CT parameters tested, three were associated significantly more often with malignant meningiomas: nodular contour (58.3% vs 26.7%), cysts (20.0% vs 4.4%) and absence of calcifications (92% vs 65.3%); none of these parameters was an absolute sign of anaplasia. Mushrooming, previously regarded as a definite sign of malignancy, was seen in 9% of benign meningiomas and in 21% of malignant ones. In angiography, no apparent differences between benign and malignant meningiomas were seen. The conclusion is that it is not possible to distinguish malignant meningiomas from benign ones with CT or angiography.     

Clinicopathological correlation of cell proliferation, apoptosis and p53 in cerebellar pilocytic astrocytomas

We have analysed 78 cerebellar pilocytic astrocytomas to assess whether histopathology, cell proliferation, apoptosis rate, p53 immunoreactivity, or flow cytometry could predict their long-term behaviour. Classic pilocytic/microcystic pattern was seen in 62 patients and 16 patients had mixed pattern with an additional non-pilocytic glial component. The overall 5-year survival was 93%, complete resection providing 100% survival. The four patients who died during the follow-up were more than 14 years of age, their primary operation had been incomplete and three of them were mixed variants. In 15 cases the tumour recurred giving a recurrence-free 5-year survival of 77%. The proliferation indices were low: Ki-67_MIB-1 (median 2.0%), PCNA (1.2%) and S-phase fraction (4.4%). The Ki-67_MIB-1-labelling index was significantly higher in young patients, but did not differ between the classic and mixed variants. Twenty-two per cent of the tumours were aneuploid with a significantly higher S-phase fraction than in diploid tumours. p53 seems to act as ardian of the genome' in pilocytic astrocytomas, because aberrant/increased expression of p53 and aneuploidy associated with enhanced apoptosis. Only patient age ( P =0.01), radicality of the primary operation ( P =0.0001) and histology (classic vs mixed, P =0.008) significantly correlated with survival. The poorer prognosis of the mixed variant suggests that this may represent a distinct entity. Although none of the novel parameters significantly predicted recurrence or survival, they indicate substantial biological variation among cerebellar pilocytic astrocytomas.     

Magnetoencephalography in presurgical evaluation of children with the Landau-Kleffner syndrome

PURPOSE: Our aim was (a) to localize the primary epileptogenic cortex for possible multiple subpial transsection in four children with the Landau-Kleffner syndrome (LKS), and (b) to evaluate the impact of magnetoencephalography (MEG) in the localizing process. Methods: We used EEG to detect the overall epileptiform activity and MEG for selective recording of fissural spikes. The cortical generators of MEG spikes were modeled with dipoles, and their activation order was determined. The voltage distribution, consistent with the earliest MEG sources, was then identified during the course of the patient's EEG spikes to determine the relative timing between stereotypic EEG and MEG spikes and to distinguish the earliest (primary) source area among the secondary ones. RESULTS: In all patients, the earliest spike activity originated in the intrasylvian cortex, spreading in one subject to the contralateral sylvian cortex within 20 ms. Secondary spikes occurred within 10-60 ms in ipsilateral perisylvian, temporooccipital, and parietooccipital areas. A single intrasylvian pacemaker initiated all epileptic activity in two patients, whereas the other two had independent left- and right-hemisphere circuits or focal spikes. MEG source dynamics predicted the results of the methohexital suppression test in two patients and was confirmed by surgery outcome in one patient, in whom all epileptic activity ceased after a small transsection of the sylvian pacemaker. CONCLUSIONS: (a) The intrasylvian cortex is a likely pacemaker of epileptic discharges in LKS, and (b) MEG provides useful presurgical information of the cortical spike dynamics in LKS patients.     

Prolactinoma of the pituitary containing amyloid

A transsphenoidal operation was performed in a 27 year old man because of a large intrasellar expansion and marked hyperprolactinaemia (33 000 mU/l). The tumour found in the operation bulged into the sphenoidal sinus and was extirpated. On histopathological examination the tumour consisted mainly of congophilic amyloid spherules with intermingled sparse adenoma cells. The adenoma cells were strongly positive for prolactin in immunoperoxidase staining, and in electron microscopy they contained secretory granules. Ultrastructurally the amyloid spherules consisted of masses of concentrical extracellular amyloid filament bundles.     

Fine tuning the correlation limit of spatio-temporal signal space separation for magnetoencephalography

Head, jaw and tongue movements contribute to speech artifacts in magnetoencephalography (MEG). Their sources lay close to MEG sensors, therefore, the spatio-temporal signal space separation method (tSSS), specifically suppressing nearby artifacts, can be used for speech artifact suppression. After data reconstruction by signal space separation (referred as SSS), tSSS identifies artifacts by their correlated temporal behavior inside and outside the sensor helmet. The artifacts to be eliminated are thresholded by the quantitative level of this correlation determined by correlation limit (CL). Unnecessarily high CL value may result in suboptimal interference suppression. We evaluated the performance of tSSS with different CLs on MEG data containing speech artifacts. MEG was recorded with 204 planar gradiometers and 102 magnetometers in two subjects counting aloud. The recorded data were processed by tSSS using CLs 0.98, 0.8 and 0.6, and traces were compared. The speech artifact was increasingly suppressed with decreasing CL, but sufficient suppression was achieved at different CL in each subject. Alpha rhythm was not suppressed with CL 0.98 or 0.8; some amplitude reduction with CL 0.6 occurred in one subject. The tSSS is a robust tool suppressing MEG artifacts. It can be fine tuned for challenging artifacts which, after insufficient rejection might resemble brain signals.     

Stem cell protein BMI-1 is an independent marker for poor prognosis in oligodendroglial tumours

Aims: The polycomb factor BMI‐1 has recently been implicated in tumorigenesis of the central nervous system in several experimental animal models. However, the significance of BMI‐1 in human glioma has not been investigated. Here we describe expression of the polycomb protein BMI‐1 and its downstream targets p16^Ink4a and MDM2 in both high‐ and low‐grade human glioma. Methods: Tumour samples were collected from 305 adult patients treated for primary grades 2–4 gliomas between 1980 and 2006 in Finland and Germany. BMI‐1, p16 and MDM2 expression was evaluated using immunohistochemistry in representative paraffin‐embedded tumour tissue. The significance of observed immunoreactivity, age at onset, gender, histopathological findings and proliferative index was analysed in univariate and multivariate survival models. Results: BMI‐1 was expressed in all histologic types of diffuse gliomas. We found a significant correlation (P = 0.007) between the frequency of BMI‐1 immunoreactive tumour cells and poor survival in World Health Organization grades II–III oligodendrogliomas and oligoastrocytomas (n = 62). The median survival of patients grouped by low, intermediate or high frequency of BMI‐1 immunoreactive tumour cells was 191 months, 151 months and 68 months, respectively. This association was also significant in the Cox multivariate regression model. Nuclear p16 immunopositivity predicted better survival in astrocytomas and an inverse correlation between p16 expression and the Ki‐67 mitotic index was also observed. Conclusions: BMI‐1 is found in all histological types of gliomas and the relative protein expression of BMI‐1 is a novel independent prognostic marker in oligodendroglial tumours.     

Peroxiredoxins and antioxidant enzymes in pilocytic astrocytomas

OBJECTIVE: Peroxiredoxins are antioxidant enzymes (AOEs), which are redox-regulated thiol proteins with potential effects on the growth, invasion and drug resistance of neoplastic cells. In this study, their biology and clinical significance were examined in pilocytic astrocytomas (PAs). MATERIAL AND METHODS: The expression of peroxiredoxins (Prx I-VI) was investigated in 105 PAs by the means of immunohistochemistry and compared with the expression of selected other antioxidant enzymes, cell proliferation, angiogenesis, apoptosis, p53, histopathology and patient survival. RESULTS: Peroxiredoxins were strongly expressed in general suggesting that oxidative damage and consequent defense takes place during the progression of pilocytic astrocytomas. In agreement with this hypothesis, several other AOEs correlated with the degenerative features and angiogenesis possibly associated with reactive oxygen species-derived cellular damage. Moreover, the expression of the AOEs was associated with each other indicating a concurrent activation of the enzymes. With the exception of manganese superoxide dismutase (MnSOD), a strong expression of AOEs was generally associated with higher cell proliferation. Prx VI seemed to have a positive association with a longer recurrence-free interval while other AOEs had no association with patient survival. Many AOEs, such as MnSOD, induce chemo- and radioresistance and are highly elevated in aggressive malignancies. PAs lack this confounding factor, and these tumors are treated only by surgery. CONCLUSIONS: Taken together, the results of this study on pilocytic astrocytomas suggest that the levels of Prxs and other AOEs and their related thiol proteins are generally strongly expressed in these tumors. At least Prx VI can contribute to tumor behavior which can make it a potential prognostic factor.