Cyclooxygenase (COX)-1 expressing macrophages/microglial cells and COX-2 expressing astrocytes accumulate during oligodendroglioma progression.

Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of edema, impeding blood flow and immunomodulation in the pathologically altered brain. Two COX iso-enzymes have been associated with brain disease, the constitutively expressed COX-1 and the cytokine-inducible COX-2. We have used single and double labeling immunohistochemistry to analyse COX-1 and COX-2 expression in twenty-six primary WHO grade II oligodendrogliomas, sixteen primary WHO grade III anaplastic oligodendrogliomas, twenty-seven matched recurrences and ten neuropathologically unaltered brains. COX-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of COX-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in primary anaplastic oligodendrogliomas (P<0.0001) and in anaplastic oligodendroglioma relapses (P=0.011). Patients with low COX-1 labeling scores in the primary tumors had significantly longer time to progression and overall survival (P=0.0285) than those with high COX-1 labeling scores. COX-2 immunoreactivity was predominantly observed in disseminated neurons and astrocytes. In glioblastoma multiforme relapses, accumulation of COX-2 expressing astrocytes was observed surrounding areas of focal necrosis. The number of COX-2 expressing astrocytes was significantly (P=0.0471) lower in primary oligodendrogliomas than in high grade oligodendroglioma relapses. These data provide convincing evidence for the differential accumulation of cyclooxygenase isoforms during oligodendroglioma progression in vivo.

Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression.

Heme oxygenase (HO-1, HSP32) catalyzes the oxidation of heme to biliverdin and carbon monoxide, a putative neurotransmitter. In the brain, HO-1 expression has been associated with neuroprotection during oxidative stress and hypoxia. However, consecutive downstream mediation is involved in neoangiogenesis and consequent neoplastic outgrowth. We have analyzed HO-1 expression in 69 oligodendroglioma tissue samples, in rat intracranially transplanted C6 gliomas, and neuropathologically unaltered control brains by immunohistochemistry. Double labeling experiments confirmed the nature of HO-1 expressing cells. Reverse transcription-polymerase chain reaction was used to demonstrate HO-1 gene expression. HO-1 immunoreactivity was predominantly observed in macrophages/microglial cells. The number of HO-1 expressing macrophages/microglial cells was significantly lower in primary oligodendrogliomas than in their matched relapses (P<0.0001) and lower in primary anaplastic oligodendrogliomas than in their relapses (P=0.0006). Prominent accumulation of HO-1 expressing macrophages/microglial cells was observed in perinecrotic areas of both experimental rat and human glioblastoma relapses. HO-1 expressing neurons, macrophages/microglial cells and astrocytes were scattered in areas of infiltrative tumor growth. Surprisingly, HO-1 mRNA was detected in only one glioblastoma multiforme relapse. We conclude from these data that HO-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression in areas of focal necrosis. However, overall biological function of this phenomenon remains to be determined.

Distinct radiochemotherapy protocols differentially influence cellular proliferation and expression of p53 and Bcl-2 in glioblastoma multiforme relapses in vivo.

Several protocols for the adjuvant treatment of glioblastoma multiforme (GBM) are currently being evaluated. In this context, little is known about the influence of radiochemotherapy on apoptosis and the expression of apoptosis-related proteins in vivo. We have analyzed the incidence of apoptosis using in situ nick translation (ISNT) and expression of Ki-67 (MIB- 1), p53 (DO-1 and DO-7), Bcl-2 and transglutaminase II (TGase II) by immunohistochemistry in 41 patients with GBM and their matched relapses. Sixteen patients received radiochemotherapy, 18 irradiation and 7 no treatment. Radiochemotherapy resulted in an increase in Bcl-2+ cells (p = 0.013). Irradiation caused the reduction of MIB-1+ (p = 0.0015), DO-7+ (p = 0.0043) and the increase of Bcl-2+ cells (p = 0.016). We calculated a positive correlation between high TGase II scores in patients preceding radiochemotherapy (p = 0.0186) and no treatment (p = 0.0158), low ISNT scores (p = 0.0018) and high DO-1 scores (p = 0.0233) in patients preceding irradiation and short time to progression. These data show that distinct postsurgical radiochemotherapy protocols differentially alter cellular proliferation and expression of p53 and Bcl-2 in GBM relapses. Furthermore, we show that ISNT, DO-I and TGase II labeling scores are therapy-specific predictors of time to progression in GBM patients.

A case of spinal glioblastoma multiforme: immunohistochemical study and review of the literature.

A 31-year old female underwent subtotal resection of a spinal glioblastoma multiforme (GBM) at level D 10/11 in June 1997. Immunohistochemistry revealed increased MIB-1 labeling index and accumulation of p53 protein. Routine MRI in February 1998 showed multiple tumors of the lumbar spinal cord. At open biopsy, diffuse infiltration of multiple radices was seen. Histologically and immunohistochemically, the tumor was similar to the primary. In May 1998, MRI revealed multiple intracranial metastases and meningeal involvement. The patient died in June 1998, 13 months after the onset of symptoms. The lifes of patients with spinal gliomas are not endangered by direct compression of the brain stem, and systemic metastases are extremely uncommon with gliomas. Yet, survival times in the reported case and in the literature are not better than with cerebral localization. Analysis of the present case and a survey of the literature indicate that CSF involvement and consecutive intracranial seeding determine the prognosis of patients with spinal GBM. Thus, regular monitoring of CSF-cytology and/or spinal MRI appear to be advisable in spinal GBM.

Intracranial inflammatory tumors: a survey of their various etiologies by presentation of 5 cases.

Due to similar clinical and neuroradiological features, intracranial inflammatory tumors (IITs) are frequently misdiagnosed as brain neoplasms, from which they notably differ in respect to therapy and prognosis. In this article, five cases of such tumors are presented. Three of the patients with brain tumors (cases 3, 4 and 5) presented a history of 'pararheumatic' syndromes but no diagnosis of defined immunopathies. On the basis of radiological findings, all processes were classified as genuine brain neoplasms, but histology showed reactive inflammatory features. The possible etiologies of these 'tumors' are discussed on the basis of all clinical and histological data of the patients. The spectrum of diseases potentially leading to the manifestation of an IIT is reviewed. Additionally, the presentation of case 5, who developed a highly malignant B-cell-lymphoma 6 months after the removal of an IIT without any histological signs of atypia, shows that this differential diagnosis always has to be kept in mind.

BCL-2 family protein expression in initial and recurrent glioblastomas: modulation by radiochemotherapy.

OBJECTIVE: In vitro studies indicate a role of apoptosis regulatory proteins of the BCL-2 family in the resistance of glioblastoma multiforme to irradiation and chemotherapy. To date, no study has compared the expression of these proteins in initial and recurrent tumours. The differences of expression of BCL-2, BCL-X, BAX, and MCL-1 proteins of paired first resection and recurrence glioblastoma specimens were examined. METHODS: Immunohistochemistry was performed in 37 cases of glioblastoma multiforme with paraffin embedded tissue from first resections and their recurrences in three treatment groups (15 radiochemotherapy, 15 irradiation, seven untreated). Ten high power fields were evaluated with an arbitrary score (< 5%=1, 5-50%=2, >50%=3), and cumulative scores for each antigen calculated. RESULTS: In the whole group, we found a significant up regulation of antiapoptotic BCL-2 (median cumulative score of 15 in the primary, 19 at recurrence; p<0.0001 in the Wilcoxon test), BCLX (median scores 20 and 25, respectively, p<0.0001), and MCL-1 (median scores 11 and 14, p=0.0395), and a significant down regulation of proapoptotic BAX (median scores 14 and 11, p<0.0001). In the subgroups, these trends were also found. No association between protein expression and treatment regimen was found, although significant changes were restricted to the subgroups that received adjuvant chemotherapy. No significant correlation with clinical prognosis was detected with the Kaplan-Meier method. CONCLUSIONS: In the development from initial to recurrent glioblastoma multiforme, the BCL-2 family rheostat shifts towards antiapoptotic adjustment in vivo. Importantly, the changes in BCL-2 family protein expression characterised here were also seen in the subgroup of patients who did not receive adjuvant radiotherapy or chemotherapy, suggesting that the changes of BCL-2 family protein expression result not only from radiochemotherapy but also reflect the natural course of disease.

Epidermoid tumor of unusual expansion at the skull base.

The case of an epidermoid tumor of unusual extension at the skull base is reported. Various and comprehensive radiologic examinations are described and the difficulty of diagnosis of rare brain-base processes is shown. Although neuroimaging with CT scan, CT cisternography, angiography and MRI was carried out on adequate diagnosis could not be made so that the question of operability could not be answered. In this case MRI did not prove to be more sensitive than other traditional radiologic examinations for the primary diagnosis, postoperative control, or clarification of suspected recurrence.

Lhermitte-Duclos disease--its minimal lesions in electron microscope data and CT findings.

Clinical, necropsy, and electron microscope findings are described for a patient with Lhermitte-Duclos disease. Evidence that the disease originated from granule cell precursors was obtained from electron microscopy and from reconstruction in step serial sections of microscopic lesions found in the contralateral cerebellar hemisphere. The latter indicate a process of proliferation and hypertrophy of granule cells at their site of origin in the superficial granular layer, along their normal path of migration, or else at their destination in the cerebellar granular layer.

Tumor-like amyloid formation (amyloidoma) in the brain.

An almost walnut-sized tumor was removed surgically from the left occipital lobe of a 46-year-old woman, who had suffered for 4 year from progressive visual loss with scotoma and finally from hemianopia, associated with attacks of headaches and recurrent episodes of depression each lasting for some weeks or months. Neuropathological examination, including polarization, thioflavine, fluorescence, immunofluorescence staining, and electron microscopy, revealed an amyloidoma, which consisted of broad appositionally grown amyloid deposits surrounded by some plasma cells, monocytic or foreign body cell types. The massive accumulations, often associated not only with blood vessels or perivascular collagenous fibers but also lying in the cerebral tissue not unlike senile plaques in the cortical gray matter corresponded to gradually growing masses as seen in the repeated CT scans. This unique lesion in the brain of a patient who did not show any evidence of systemic disorder, seems to confirm that the spontaneous tumor-like amyloid, which gave an immunofluorescent staining mainly with anti-IgM, is a special variant of primary amyloidosis (amyloid L) or of so-called paramyloid.

Anterior cervical fusion after traumatic dislocation of the cervical spine in childhood and adolescence.

5 patients aged 11-16 years with traumatic lesions of the cervical spine are reported. 4 patients were treated by operative ventral fusion with good results. Regarding the preoperative history of these 4 patients and the history of another 1 treated by conservative means, the authors tend to relatively early operative ventral fusion.