Liberski Pp

Glioma cells showing IDH1 mutation cannot be propagated in standard cell culture conditions.

Background:It has recently been reported by several sources that original (i.e., present in vivo) glioma cell phenotypes or genotypes cannot be maintained in vitro. For example, glioblastoma cell lines presenting EGFR amplification cannot be established.Methods and results:IDH1 sequencing and loss of heterozygosity analysis was performed for 15 surgery samples of astrocytoma and early and late passages of cells derived from those and for 11 archival samples. We were not able to culture tumour cells presenting IDH1 mutations originating from currently proceeded 10 tumours; the same results were observed in 7 samples of archival material.Conclusion:The IDH1 mutation is expected to be almost mutually exclusive with EGFR amplification, so glioma cells with IDH1 mutations seem to represent a new group of tumour cells, which cannot be readily analysed in vitro because of their elimination. The reasons for this intriguing phenomenon should be investigated since its understanding can help to define a new therapeutic approach based on simulating in vivo conditions, responsible for tumour cells elimination in vitro. Moreover, a new model for culturing glioma cells in vitro should be designed since the current one does not provide conditions corresponding to in vivo growth.

Ultrastructural Pathology of Glial Brain Tumors Revisited: A Review

The ultrastructural pathology of primary brain tumors of glial origin is examined. These are divided into two major groups. The first category comprises astrocytoma with the variants: fibrillary, protoplasmic, gemistocytic, and anaplastic. These are biologically aggressive tumors of a relatively high proliferative potential and include a substantial proportion of cases that transform into the most malignant secondary glioblastoma. The second category, comprised of rather benign tumors of a limited proliferative capacity and a reasonable good prognosis, includes such clinico-pathological entities as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and subependymal giant cell astrocytoma of tuberous sclerosis. There is no ultrastructural feature, however, which makes it possible to discriminate between major subclasses of astrocytes; but secondary glioblastoma cells, while still retaining the stigmata of neoplastic astrocytes, are characterized by nuclei that seem to be more indented, cisterns of the endoplastic reticulum may be distended, and intranuclear pseudoinclusions are frequently observed. Primary glioblastoma, which probably originates de novo, is characterized by poorly differentiated cells with a paucity of subcellular organelles and no obvious features of astrocytic origin. Granular cell tumor also belongs to neoplasms of astrocytic lineage and the hallmark of this entity is a cell characterized by the presence of numerous membrane-bound, electron-dense autophagic vacuoles. Its malignant analogue is the granular cell glioblastoma. Two subtypes of granular cell glioblastoma have been distinguished. The first is characterized by the presence of numerous granular, electron-dense bodies which correspond to autophagic vacuoles. The second type is characterized by numerous electron-dense, amorphous masses within cellular processes. These electron-dense inclusions are virtually indistinguishable from minute Rosenthal fibers. The pilocytic astrocytoma is virtually indistinguishable at the ultrastructural level from fibrillary astrocytomas but cells tend to be more elongated. Besides Rosenthal fibers, two types of distinctive structures are relatively common in pilocytic astrocytomas: eosinophilic hyaline droplets and round granular bodies, which are composed of large aggregates of electron-dense secondary lysosomes or small electron-dense bodies, respectively. Pleomorphic xanthoastrocytoma is characterized by astrocytes surrounded by basal membranes. It belongs to a peculiar category of astrocytic desmoplastic brain tumors occurring in younger patients, the common denominator for which is the presence of basal lamina. The last category in this group is subependymal giant cell astrocytoma, a tumor of bivalent (glial and neuronal) differentiation, the cells of which are characterized by the presence of peculiar crystalloids. The hallmark of oligodendroglioma is the presence of concentric arrays of membranes (so-called membrane laminations, whorls, or scrolls). A fragment of the cytoplasm sequestrated within a particular whorl may contain mitochondria, lysosomes, or abundant glycogen granules. Ependymomas are characterized by a florid picture dominated by the presence of microlumina, cilia with basal bodies (blepharoplasts), microvilli, and long, interdigitating intercellular junctions of the zonulae adherentiae type. Ganglioglioma, the last category covered by this review, is a mixed glio-neuronal tumor. While glial cells are indistinguishable from their counterparts encountered elsewhere (mostly pilocytic astrocytes), the ganglion cells are characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments, and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers is seen. Dense-core vesicles are pleomorphic and ranged in a diameter from small synaptic vesicles to large lysosome-like neurosecretory granules.

Ultra Structural Pathology of Gerstmann-Sträussler-Scheinker Disease

We report a detailed ultrastructural study based on a large series of samples from a recent case of Gerstmann-Sträussler-Scheinker disease from the original Austrian family. Numerous PrP-immunopositive plaques dominated light microscopic neuropathology. Ultrastructurally, several types of plaques were observed: unicentric kuru, multicentric, and neuritic. Dystrophic neurites accompanied amyloid plaques to differing degrees. Plaques were enveloped by astrocytic processes and invaded by microglial cells. A prominent astrocytic reaction accompanied abundant spongiform change. Unusual crystalloids were observed in mitochondria while another type of crystalloid was seen within lysosomes. We conclude that Gerstmann-Sträussler-Scheinker disease is distinct also at the ultrastructural level.

Cytogenetic Changes in Two Cases of Subependymal Giant-Cell Astrocytoma

Cytogenetic analysis of subependymal giant-cell astrocytomas (SEGAs) from two patients presenting the clinical symptoms of tuberous sclerosis complex (TSC) revealed clonal chromosomal changes, resulting in the partial loss of chromosome 22q in both tumors. Immunohistochemically, tumors exhibited features of glial differentiation, while ultrastructural studies identified the characteristic paracrystalline inclusions within the tumor cells. To our knowledge, it is the first cytogenetic description of SEGAs associated with TSC.

Ultrastructural heterogeneity of gangliogliomas.

Gangliogliomas are rare brain tumors, composed of neuronal and glial cells mixed in a different proportion. The basic histopathological pattern of gangliogliomas is well recognized but the variable microscopic appearance still can pose a challenge to the neuropathologist. The authors reanalyzed their series of gangliogliomas in the files of two departments of neuropathology. All analyzed tumors fulfilled the WHO histological criteria of ganglioglioma. Seven tumors were examined by electron microscopy. The following ultrastructural features were graded: presence of dense-cored vesicles, synaptic vesicles, synapses and intermediate filaments, abundant basal membranes, dystrophic neurites, autophagic vacuoles, and multivesicular bodies. Most of the neoplastic neurons were large, polyglonal or oval with well-developed subcellular organelles, round nuclei, and prominent nucleoli. In most cases there were abundant dense core vesicles, observed in both the tumor cell bodies as well as in their processes. Synapses were typically observed. Intermediate filaments were abundant in all tumors. The most intriguing ultrastructural finding was abundant presence of autophagic vacuoles. In 4 cases, multivesicular bodies were observed. All of the tumors with multivesicular bodies also contained abundant autophagic vacuoles.

Novel Gene Expression Model for Outcome Prediction in Paediatric Medulloblastoma

Medulloblastoma is the most frequent type of embryonal tumour in the paediatric population. The disease progression in patients with this tumour may be connected with the presence of stem/tumour-initiating cells, but the precise source and characteristics of such cells is still a subject of debate. Thus, we tried to analyse biomarkers for which a connection with the presence of stem/tumour-initiating cells was suggested. We evaluated the transcriptional level of the ATOH1, FUT4, NGFR, OTX1, OTX2, PROM1 and SOX1 genes in 48 samples of medulloblastoma and analysed their usefulness in the prediction of disease outcome. The analyses showed a strong correlation of PROM1, ATOH1 and OTX1 gene expression levels with the outcome (pu2009≤u20090.2). On the basis of the multivariate Cox regression analysis, we propose a three-gene model predicting risk of the disease, calculated as follows:

Autophagy is a common ultrastructural feature of neuropathology of prion diseases

mathrm{RS}left( {mathrm{risk};mathrm{score}} right)=left( {0.81times PROM1} right)+left( {0.18times OTX1} right)+left( {0.02times ATOH1} right)

Mutational analysis of hSNF5/INI1 and TP53 genes in choroid plexus carcinomas

. Survival analysis revealed a better outcome among standard-risk patients, with a 5-year survival rate of 65xa0%, compared to the 40xa0% rate observed among high-risk patients. The most promising advantage of such molecular analysis consists in the identification of molecular markers influencing clinical behaviour, which may in turn be useful in therapy optimization.