Topical Review Article: Medulloblastoma: II. A Pathobiologic Overview

Tomlinson, Francis H.; Scheithauer, Bernd W.; Jenkins, Robert B.

doi:10.1177/088307389200700302

Cited by 15 publications

(7 citation statements)

References 97 publications

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“…Histologically identical tumors may arise in the pineal region, cerebrum, spinal cord, or brainstem and various classification systems assign names to these tumors based on their location (eg, pineoblastoma and cerebral neuroblastoma). Recognition that some PNETs contain cclls with the histological characteristics of neurons, glial cells (including ependyma), and, in rare instances, inuscle or melanocytes [2,29,[44][45][46][47] led to tumor nomenclature based on these characteristics [ 51. irrespective of the method of fixation [33,34,491. We found that the biological characteristics of PNETs are as prognostically significant as their clinical features (eg, tumor location and metastatic stage).…”

Section: Discussionmentioning

confidence: 99%

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Janss

Yachnis

Silber

et al. 1996

Annals of Neurology

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Primitive neuroectodermal tumors (PNETs) of the central nervous system, including medulloblastomas (PNET/MB), are the most common malignant brain tumor of childhood. These tumors often express proteins characteristic of glial differentiation (glial fibrillary acidic protein, GFAP), neuronal differentiation (neurofilament proteins, NFPs), and/or photoreceptor differentiation (retinal-S antigen). To identify biological factors of prognostic significance in PNETs, the expression of glial, neuronal, or photoreceptor antigens was evaluated in the tumor specimens of 86 patients with PNETs by immunohistochemistry after microwave antigen enhancement. Patterns of differentiation were then compared with patient relapse-free survival. Multivariate analysis of PNET immunohistochemistry and clinical variables indicated GFAP expression conferred a 6.7-fold greater risk of relapse than tumors that did not express GFAP or NFPs. Increased risk of relapse was directly related to the amount of GFAP expression. Tumors exhibiting clumps or sheets of GFAP-staining cells were associated with a 3.0-fold increased risk of relapse compared with tumors that did not express GFAP, irrespective of immunohistochemical evidence of other differentiation, while scattered GFAP staining was not associated with increased risk of relapse. These findings indicate that expression of GFAP in PNETs has prognostic power comparable with the most significant clinical factors currently used to predict clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Janss

Yachnis

Silber

et al. 1996

Annals of Neurology

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“…The supratentorial PNET (stPNET) displays very similar histological features; therefore, both tumors have been proposed to represent a distinct biological entity (Rorke et al, 1985;World Health Organization, 1994). Medulloblastomas are believed to originate from the external granular layer of the cerebellum (Tomlinson et al, 1992;Kozmik et al, 1995); however, so far, little is known about the molecular mechanisms that induce neoplastic transformation of this immature neuronal stem cell.…”

Section: Introductionmentioning

confidence: 99%

High-resolution deletion mapping of chromosome arm 17p in childhood primitive neuroectodermal tumors reveals a common chromosomal disruption within the Smith-Magenis region, an unstable region in chromosome band 17p11.2

Scheurlen

Seranski

Mincheva

et al. 1997

Genes Chromosom. Cancer

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Loss of heterozygosity (LOH) on chromosome arm 17p is the most common genetic aberration in childhood primitive neuroectodermal tumors (PNETs). To determine the frequency and extent of 17p deletions, 29 loci on 17p were investigated in 24 tumors by using restriction fragment length polymorphism (RFLP) and microsatellite analysis. LOH on 17p was found in 9 of 24 tumors. In all tumors with LOH, a continuous stretch from the telomere to chromosome band 17p11.2 was completely deleted, and no interstitial or terminal small‐scale deletions were detected in the remaining 15 tumors. In four tumors with LOH on 17p, the chromosomal breakpoint was located between D17S953 and D17S805. To identify this deletion breakpoint on the cytogenetic map of chromosome 17 and to exclude uniparental disomy, we verified our data by using fluorescence in situ hybridization (FISH) analyses. By using two yeast artificial chromosome (YAC) clones that were positive for D17S689 and D17S953, the same breakpoint was confirmed in two specimens of cerebrospinal fluid (CSF) metastases by using FISH on interphase preparations. We demonstrate that, in most childhood PNETs with LOH on 17p, the breakpoint is close to, but not within, the centromere. It varies, and it occurs predominantly between the two markers D17S689 and D17S953, which is an unstable chromosomal region that is deleted or duplicated in the Smith‐Magenis syndrome. Because LOH of 17p is associated with the formation of isochromosome 17q in the majority of PNETs, this study provides entry points to determine the molecular nature of this phenomenon. Genes Chromosom. Cancer 18:50–58, 1997. © 1997 Wiley‐Liss, Inc.

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“…More than 90% of cases of CNS PNET occur in the posterior fossa as medulloblastomas. PNETs at other CNS sites resemble the classic medulloblastoma, which has a propensity for divergent differentiation along neuro-epithelial lines, manifesting as expression of glial fibrillary acidic protein (GFAP) and/or neuronal proteins or rarely as the presence of scattered ganglion cells (Tomlinson et al, 1992;Ellison and Love, 1998). In addition to the classic medulloblastoma, several variants are recognized in the World Health Organization classification of CNS tumours: desmoplastic medulloblastoma, melanotic medulloblastoma and medullomyoblastoma (Kleihues et al, 1993).…”

mentioning

confidence: 99%

“…In addition to the classic medulloblastoma, several variants are recognized in the World Health Organization classification of CNS tumours: desmoplastic medulloblastoma, melanotic medulloblastoma and medullomyoblastoma (Kleihues et al, 1993). Desmoplastic medulloblastomas account for approximately 20% of medulloblastomas and frequently exhibit a nodular architecture in which cells often show a neuronal or glial immunophenotype; these nodular/desmoplastic medulloblastomas are considered to form a histological spectrum of tumours, distinct from classic medulloblastomas (Giangaspero et al, 1991;Tomlinson et al, 1992).…”

mentioning

confidence: 99%

Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours

et al. 1999

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SummaryThe objective of this study was to test the hypothesis that chromosomal imbalances in central nervous system primitive neuroectodermal tumours (PNETs) reflect site and histology. We used comparative genomic hybridization to study 37 cases of PNET, of which four were cerebral and 31 were medulloblastomas classified histologically as classic (n = 17) or nodular/desmoplastic (n = 14). Tumour immunophenotype was characterized with antibodies to neuroglial, mesenchymal and epithelial markers. Chromosomal imbalances were detected in 28 medulloblastomas (90%), and significant associations between tumour variants and genetic abnormalities were demonstrated. Aberrations suggesting isochromosome 17q were present in eight (26%) medulloblastomas, of which seven were classic variants. None of these cases, or a further six with gain of 17q, showed immunoreactivity for glial fibrillary acidic protein. Loss on 9q was found in six cases (19%), five of them nodular/desmoplastic. Loss of 22 occurred in four (13%), all classic medulloblastomas in young patients with a poor outcome and immunoreactivity for more than one epithelial or mesenchymal marker. Different patterns of imbalance were found in the cerebral PNETs. There were no abnormalities of chromosome 17, but all three cases with imbalance showed losses of 3p12.3-p14.

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Topical Review Article: Medulloblastoma: II. A Pathobiologic Overview

Cited by 15 publications

References 97 publications

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

Glial differentiation predicts poor clinical outcome in primitive neuroectodermal brain tumors

High-resolution deletion mapping of chromosome arm 17p in childhood primitive neuroectodermal tumors reveals a common chromosomal disruption within the Smith-Magenis region, an unstable region in chromosome band 17p11.2

Comparative genomic hybridization and histological variation in primitive neuroectodermal tumours

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