Assessment of candidate immunohistochemical prognostic markers of meningioma recurrence.

Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely resected tumours.

Clinical, radiological and pathological correlates of leukoaraiosis.

INTRODUCTION: Leukoaraiosis is characterized by an abnormal appearance of the brain white matter on imaging. Its pathogenesis is still a matter of investigation. The purpose of this study was to investigate the radiological, clinical and pathological correlates of leukoaraiosis. METHODS: The study population consisted of 93 deceased patients. The pre-mortem T2W magnetic resonance images were evaluated for the presence and grading of leukoaraiosis. The clinical and pathological characteristics based on the clinical charts and autopsy reports were evaluated. Tissue specimens of the blocks of 19 brains that demonstrated severe leukoaraiosis and those of five control brains were excised and stained. RESULTS: The variables found to be significantly associated with leukoaraiosis were age and a clinical history of Parkinson's disease. Other risk factors and pathological markers of atherosclerosis were not significantly correlated with leukoaraiosis. No significant difference was found between the scoring of the myelin integrity, glial fibrillary acidic protein, cluster of differentiation 68 and smooth muscle actin. There was a significant difference with respect to thickening of vessels walls. CONCLUSIONS: Our pathological results indicate that structural vascular abnormalities characterized by vessel wall thickening are associated with leukoaraiosis, supporting the assertion that vascular changes and ischemia generate leukoaraiosis. The relations between parkinsonism and leukoaraiosis may be explicable through vascular effects on the circuitry of the basal ganglia.

Role of cerebral amyloid angiopathy in intracerebral hemorrhage in hypertensive patients.

OBJECTIVE: To assess the interaction of cerebral amyloid angiopathy (CAA) and arterial hypertension as cofactors for intracerebral hemorrhage (ICH). METHODS: The authors investigated 129 postmortem brains of hypertensive patients with and without ICH. Sixty-four patients had had deep (n = 40) or lobar (n = 24) ICH. Sixty-five patients without ICH served as controls. Established risk factors for ICH (age, gender, severity of hypertension, bleeding disorders, intake of anticoagulants, and chronic alcoholism) were identified from medical records. Four specimens per brain were stained with hematoxylin-eosin and Congo red. The entire ICH cohort and subgroups were compared with controls using single-factor and multiple logistic regression analyses. RESULTS: CAA was found in 15 of 64 subjects (23%) with ICH and in five of 65 controls (8%; p = 0.026). In single-factor analysis, CAA was more prevalent in lobar ICH compared with controls (p = 0.007) but not in deep ICH. Poor control of hypertension was more prevalent in the entire ICH group (p = 0.01) and in deep ICH (p = 0.016) but not in lobar ICH. ICH was predictive of the presence of CAA (odds ratio: 5.6, 95% CI: 1.8 to 19.5, p = 0.003), and CAA was more likely to be found in lobar ICH in multivariable-adjusted analysis. After adjustment for conventional risk factors, there was a weak association between CAA and deep ICH. CONCLUSION: Cerebral amyloid angiopathy plays a major role in the pathogenesis of intracerebral hemorrhage even in patients with more evident risk factors.

TER94, a Drosophila homolog of the membrane fusion protein CDC48/p97, is accumulated in nonproliferating cells: in the reproductive organs and in the brain of the imago.

We have cloned a Drosophila homolog of the membrane fusion protein CDC48/p97. The open reading frame of the Drosophila homolog encodes an 801 amino acid long protein (TER94), which shows high similarity to the known CDC48/p97 sequences. The chromosomal position of TER94 is 46 C/D. TER94 is expressed in embryo, in pupae and in imago, but is suppressed in larva. In the imago, the immunoreactivity was exclusively present in the head and in the gonads of both sexes. In the head the most striking staining was observed in the entire neuropil of the mushroom body and in the antennal glomeruli. Besides TER94, sex-specific forms were also detected in the gonads of the imago: p47 in the ovaries and p98 in the testis. TER94/p47 staining was observed in the nurse cells and often in the oöcytes, while TER94/p98 staining was present in the sperm bundles. On the basis of its distribution we suggest that TER94 functions in the protein transport utilizing endoplasmic reticulum and Golgi derived vesicles.