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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Brain Tumor - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11396737
AU - Burtscher IM; Holtas S
TI -
Proton magnetic resonance spectroscopy in brain tumours: clinical
applications.
SO - Neuroradiology 2001 May;43(5):345-52
AD - Department of Diagnostic Radiology, University Hospital, Lund, Sweden.
isabella.burtscher@drad.lu.se
Parallel to the rapid development of clinical MRI, MR spectroscopy (MRS)
has, after starting as an analytical tool used in chemistry and physics,
evolved to a noninvasive clinical examination. Most common
neuroradiological diagnostic indications for MRS are functional inborn
errors, neonatal hypoxia, ischaemia, metabolic diseases, white matter
and degenerative diseases, epilepsy, inflammation, infections and
intracranial neoplasm. Compared to CT and MRI, well-established
morphological diagnostic tools, MRS provides information on the
metabolic state of brain tissue. We review the clinical impact of MRS in
diagnosis of tumours and their differentiation from non-neoplastic
lesions.
2
UI - 11396738
AU - Kaminogo M; Ishimaru H; Morikawa M; Ochi M; Ushijima R; Tani M; Matsuo
TI -
Y; Kawakubo J; Shibata S
Diagnostic potential of short echo time MR spectroscopy of gliomas with
single-voxel and point-resolved spatially localised proton spectroscopy
of brain.
SO - Neuroradiology 2001 May;43(5):353-63
AD - Department of Neurosurgery, Nagasaki University School of Medicine,
Japan. kaminogo@net.nagasaki-u.ac.jp
Accurate neuroimaging grading of gliomas is useful for management, but
techniques such as MRI and CT are not sufficiently reliable. Necrosis is
a consistent, decisive prognostic factor and the key diagnostic
criterion for glioblastoma multiforme. MR spectroscopy (MRS) allows
noninvasive measurement of metabolites in brain tumours and mobile
lipids reflect necrosis. However, short echo-time (TE) spectroscopy has
been required for reliable assessment of lipids, since their relaxation
times are very short. Recent advances have made it possible to perform
short-TE MRS. We attempted to evaluate the significance of short TE
spectroscopy as part of routine imaging for diagnosis and grading of
gliomas. We performed TE 30 ms MRS in 25 patients with gliomas (grade II
six; grade III three; grade IV, 16) and in 19 areas of healthy white
matter using proton brain examination/single voxel (PROBE/SV) and
point-resolved spatially localised spectroscopy (PRESS). With short-TE
spectroscopy, lipid signals were detected in all 16 tumours of grade IV,
one grade II (P = 0.0002) and none of grade III (P = 0.001). TE 136 ms
MRS, carried out in 20 of these cases, showed lipid signals in only four
of 14 grade IV tumours and in none of the other six.
N-acetylaspartate/choline (NAA/Cho) ratios were always more than 1.0 in
healthy tissues and less than 1.0 in all but one of the gliomas. The
mean creatine (Cr)/Cho ratio in each tumour grade was significantly
lower than in the healthy tissues. The mean Cr/Cho ratio was also
significantly lower in grade IV than in grade II tumours (P < .0005).
Considerable overlap in Cr/Cho ratio was observed between grade II and
grades III and IV gliomas at long but less so at short-TE MRS. We
conclude that short-TE MRS with PROBE/SV and PRESS is of value in
grading gliomas.
3
UI - 11891207
AU - Rickert CH; Wiestler OD; Paulus W
TI -
Chromosomal imbalances in choroid plexus tumors.
SO - Am J Pathol 2002 Mar;160(3):1105-13
AD - Institute of Neuropathology, University Hospital Munster, Munster,
Germany. rickchr@uni-muenster.de
We studied 49 choroid plexus tumors by comparative genomic
hybridization. Chromosomal imbalances were found in 32 of 34 choroid
plexus papillomas and 15 of 15 choroid plexus carcinomas. Choroid plexus
papillomas frequently showed +7q (65%), +5q (62%), +7p (59%), +5p (56%),
+9p (50%), +9q (41%), +12p, +12q (38%), and +8q (35%) as well as -10q
(56%), -10p, and -22q (47%); choroid plexus carcinomas mainly showed
+12p, +12q, +20p (60%), +1, +4q, +20q (53%), +4p (47%), +8q, +14q (40%),
+7q, +9p, +21 (33%) as well as -22q (73%), -5q (40%), -5p, and -18q
(33%). Several chromosomal imbalance differences could be found that
were characteristic for a tumor entity or age group. In choroid plexus
papillomas +5q, +6q, +7q, +9q, +15q, +18q, and -21q were significantly
more common whereas choroid plexus carcinomas were characterized by +1,
+4q, +10, +14q, +20q, +21q, -5q, -9p, -11, -15q, and -18q. Among choroid
plexus papillomas, children more often showed +8q, +14q, +12, and +20q;
adults mainly presented with +5q, +6q, +15q, +18q, and -22q. Although
the number of aberrations overall as well as of gains and losses on
their own bore no significance on survival among choroid plexus tumors,
a significantly longer survival among patients with choroid plexus
carcinomas was associated with +9p and -10q. Our results show that
aberrations differ between choroid plexus papillomas and choroid plexus
carcinomas as well as between pediatric and adult choroid plexus
papillomas, supporting the notion of different genetic pathways.
Furthermore, gain of 9p and loss of 10q seem to be correlated with a
more favorable prognosis in choroid plexus carcinomas.
4
UI - 11902524
AU - Lee JA
TI -
A paradox of progress.
SO - Lancet Oncol 2002 Feb;3(2):126
AD - Department of Histopathology, Rotherham General Hospital, UK.
5
UI - 11870182
AU - Stupp R; Dietrich PY; Ostermann Kraljevic S; Pica A; Maillard I; Maeder
TI -
P; Meuli R; Janzer R; Pizzolato G; Miralbell R; Porchet F; Regli L; de
Tribolet N; Mirimanoff RO; Leyvraz S
Promising survival for patients with newly diagnosed glioblastoma
multiforme treated with concomitant radiation plus temozolomide followed
by adjuvant temozolomide.
SO - J Clin Oncol 2002 Mar 1;20(5):1375-82
AD - Department of Medical Oncology, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland. roger.stupp@chuv.hospvc.ch
PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated
efficacy as second-line therapy for patients with recurrent anaplastic
astrocytoma and glioblastoma multiforme (GBM). This phase II study was
performed to determine the safety, tolerability, and efficacy of
concomitant radiation plus temozolomide therapy followed by adjuvant
temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND
METHODS: Sixty-four patients were enrolled onto this open-label, phase
II trial. Temozolomide (75 mg/m(2)/d x 7 d/wk for 6 weeks) was
administered orally concomitant with fractionated radiotherapy (60 Gy
total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide
monotherapy (200 mg/m(2)/d x 5 days, every 28 days for six cycles). The
primary end points were safety and tolerability, and the secondary end
point was overall survival. RESULTS: Concomitant radiation plus
temozolomide therapy was safe and well tolerated. Nonhematologic
toxicities were rare and mild to moderate in severity. During the
concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia,
or both were observed in 6% of patients, including two severe infections
with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of
cycles were associated with grade 3 and 4 neutropenia or
thrombocytopenia, respectively. Median survival was 16 months, and the
1- and 2-year survival rates were 58% and 31%, respectively. Patients
younger than 50 years old and patients who underwent debulking surgery
had the best survival outcome. CONCLUSION: Continuous daily temozolomide
and concomitant radiation is safe. This regimen of concomitant
chemoradiotherapy followed by adjuvant chemotherapy may prolong the
survival of patients with glioblastoma. Further investigation is
warranted, and a randomized trial is ongoing.
6
UI - 11792039
AU - Nagamachi S; Jinnouchi S; Nabeshima K; Nishii R; Flores L 2nd; Kodama T;
TI -
Kawai K; Tamura S; Yokogami K; Samejima T; Wakisaka S
The correlation between 99mTc-MIBI uptake and MIB-1 as a nuclear
proliferation marker in glioma--a comparative study with 201Tl.
SO - Neuroradiology 2001 Dec;43(12):1023-30
AD - Department of Radiology, Miyazaki Medical College, Japan.
snagama@post1.miyazaki-med.ac.jp
Technetium-99m methoxy-isobutylisonitrile (MIBI), like thallium-201
(201Tl), is a highly efficient agent for the diagnosis and monitoring of
glioma tumors. Although 201Tl uptake is known to be partly associated
with proliferative activity, little is known about the correlation
between MIBI uptake and proliferation activity in gliomas. The current
study was performed to assess the correlation between MIBI uptake and
proliferative activities in gliomas, estimated by the monoclonal
antibody to Ki-67 antigen (MIB-1) staining method. By comparing the
results with those of 201Tl, we determined which tracer would be
suitable for estimating proliferative activities. Twenty-four
presurgical glioma patients (six with low-grade gliomas, five with
anaplastic astrocytomas, and 13 with glioblastomas) were given MIBI and
201Tl SPECT. Early (10 min after injection) and delayed images (3 h
after injection) were obtained for both MIBI and 201Tl scintigraphy.
SPECT parameters, early ratio (ER), delayed ratio (DR), and retention
index (RI) were obtained in both radiopharmaceuticals. All patients
underwent subsequent surgical excision, and the specimens were
immunostained for MIB-1. The proliferative activity was measured as a
percentage positive nuclear area for MIB-1 (MI; MIB-1 index). To
evaluate the relationship between the proliferative activity and SPECT
parameters, we performed a correlation analysis. MI correlated with the
MIBI uptake ratio (r = 0.75 for ER, and r = 0.7 for DR). Both DR and RI
of 201Tl also correlated with MI, but weakly (r = 0.6 for DR, and. r =
0.59 for RI). There was no significant correlation between the MIB-1
index and the other parameters. MIBI-uptake parameters demonstrated a
stronger positive correlation with the MIB-1 index than that of 201Tl.
With the use of MIBI SPECT, we can estimate the proliferative activity
of glioma noninvasively.
7
UI - 10584843
AU - Giangaspero F; Perilongo G; Fondelli MP; Brisigotti M; Carollo C;
TI -
Burnelli R; Burger PC; Garre ML
Medulloblastoma with extensive nodularity: a variant with favorable
prognosis.
SO - J Neurosurg 1999 Dec;91(6):971-7
AD - Service of Anatomical Pathology, Ospedale Bufalini, Cesena, Italy.
OBJECT: Some medulloblastomas (MBs) are characterized by extreme
nodularity and intranodular nuclear uniformity in a fine fibrillary
background. These lesions have also been designated as "cerebellar
neuroblastoma." Although numerous reports have been published in which
their morphological features have been investigated, only a few studies
have been focused on their neuroradiological appearance, biological
behavior, and response to therapy. The goal of this study was to gather
more information about these lesions. METHODS: The authors present 11
cases of MB with extensive nodularity. Five patients were boys and six
were girls; all but one were 24 months of age or younger at diagnosis.
Magnetic resonance imaging disclosed a peculiar grapelike architecture
in eight cases. Surgical tumor removal was complete in nine cases and
partial in one. In the other case a biopsy sample of the tumor was
obtained after a preoperative course of chemotherapy. After surgery, two
children were treated with radiotherapy alone and one with craniospinal
irradiation followed by systemic chemotherapy. Eight patients were
treated with chemotherapy only. All the patients in the study are
presently alive with a median follow up of 66 months. Eight patients
(73%) are in complete remission at 35 to 156 months. Three patients
treated with chemotherapy alone postsurgery relapsed; however, all
underwent successful retreatment (two with craniospinal irradiation and
one with further surgery plus high-dose chemotherapy) and are in
complete remission. A review of the literature revealed that patients in
11 of 12 reported cases were younger than 3 years of age and that seven
of eight in whom follow-up information was available were alive and
well, with survival times ranging from 6 to 84 months. CONCLUSIONS:
Medulloblastomas with extensive nodularity represent a variant that is
characterized by: 1) occurrence in very young children; 2) a peculiar
grapelike appearance on neuroimaging; and 3) an apparently favorable
outcome.
8
UI - 11801556
AU - Burton EC; Lamborn KR; Forsyth P; Scott J; O'Campo J; Uyehara-Lock J;
TI -
Prados M; Berger M; Passe S; Uhm J; O'Neill BP; Jenkins RB; Aldape KD
Aberrant p53, mdm2, and proliferation differ in glioblastomas from
long-term compared with typical survivors.
SO - Clin Cancer Res 2002 Jan;8(1):180-7
AD - Department of Pathology, University of California, San Francisco, San
Francisco, California 94143, USA.
PURPOSE: Glioblastoma multiforme (GBM) is a highly lethal neoplasm with
a median survival of approximately 1 year. Only 2-5% of patients
originally diagnosed with GBM will survive > or = 3 years. Whether
tumors from these long-term survivors (LTSs) exhibit molecular genetic
differences compared with typical GBM survivors is not known.
EXPERIMENTAL DESIGN: Tumors from 41 patients initially diagnosed with
GBM and having survival > or = 3 years (LTS) was compared with 48 GBMs
from short-term survivors (STSs, survival < or = 1.5 years) for p53
aberrations (expression/mutation), epidermal growth factor receptor
overexpression, mdm2 overexpression, and proliferation index. RESULTS:
Nuclear p53 expression was significantly more frequent in the LTS group.
However, no difference in the rate of p53 mutation was evident.
Overexpression of epidermal growth factor receptor was slightly more
frequent in the STS patients, but this is not statistically different.
mdm2 overexpression was significantly more frequent in the STSs, and
this group had a significantly higher median proliferation index.
CONCLUSION: Long-term GBM survivors were more likely to have
p53-overexpressing tumors, although a difference in p53 mutation rate
could not be detected. They were less likely to exhibit mdm2
overexpression and had a lower proliferation rate compared with typical
GBM survivors.
9
UI - 11801559
AU - Ueki K; Nishikawa R; Nakazato Y; Hirose T; Hirato J; Funada N; Fujimaki
TI -
T; Hojo S; Kubo O; Ide T; Usui M; Ochiai C; Ito S; Takahashi H; Mukasa
A; Asai A; Kirino T
Correlation of histology and molecular genetic analysis of 1p, 19q, 10q,
TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial
tumors.
SO - Clin Cancer Res 2002 Jan;8(1):196-201
AD - Department of Neurosurgery, University of Tokyo Hospital, Tokyo
113-8655, Japan. kueki-tky@umin.ac.jp
PURPOSE: The histological diagnosis of human gliomas is of great
importance for estimating patient prognosis and guiding therapy but
suffers from being subjective and, therefore, variable. We hypothesized
that molecular genetic analysis could provide a more objective means to
classify tumors and, thus, reduce diagnostic variability. EXPERIMENTAL
DESIGN: We performed molecular genetic analysis on 91 nonselected
gliomas for 1p, 19q, 10q, TP53, epidermal growth factor receptor, and
cyclin-dependent kinase 4 abnormalities and compared with the consensus
diagnoses established among four independent neuropathologists. RESULTS:
There were six astrocytomas, seven anaplastic astrocytomas, 45
glioblastomas, 21 oligodendrogliomas, eight anaplastic
oligodendrogliomas, three oligoastrocytomas, and one anaplastic
oligoastrocytoma. Twenty-nine cases had either 1p or 19qloss of
heterozygosity (LOH) while retaining both copies of 10q, of which 25
(86%) were histologically oligodendroglioma, anaplastic
oligodendroglioma, oligoastrocytoma, or anaplastic oligoastrocytoma. As
for the oligodendroglial tumors, unanimous agreement of the initial
diagnoses was almost restricted to those cases with combined 1p/19qLOH,
whereas all nine tumors without 1p loss initially received variable
diagnoses. Interestingly, TP53 mutation was inversely related to 1pLOH
in all gliomas (P = 0.0003) but not 19qLOH (P = 0.15). CONCLUSIONS:
These data demonstrate that molecular genetic analysis of
1p/19q/10q/TP53 has significant diagnostic value, especially in
detecting oligodendroglial tumors. In addition, 1pLOH and TP53 mutations
in gliomas may be markers of oligodendroglial and astrocytic pathways,
respectively, which may separate gliomas with the same histological
diagnosis, especially oligodendroglial tumors and glioblastomas. Testing
for those molecular genetic alterations would be essential to obtain
more homogeneous sets of gliomas for the future clinical studies.
10
UI - 11555594
AU - Calogero A; Arcella A; De Gregorio G; Porcellini A; Mercola D; Liu C;
TI -
Lombari V; Zani M; Giannini G; Gagliardi FM; Caruso R; Gulino A; Frati
L; Ragona G
The early growth response gene EGR-1 behaves as a suppressor gene that
is down-regulated independent of ARF/Mdm2 but not p53 alterations in
fresh human gliomas.
SO - Clin Cancer Res 2001 Sep;7(9):2788-96
AD - Department of Molecular Pathology, Istituto di Ricovero e Cura a
Carattere Scientifico Neuromed, Pozzilli, 86077 Italy.
calognant@neuromed.it
PURPOSE: EGR-1 is an immediate early gene with diverse functions that
include the suppression of growth. EGR-1 is down-regulated many cancer
cell types, suggesting a tumor suppressor role, and may critically
involve the p53 pathway. The aim of this work was to measure the
expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in
fresh human gliomas. EXPERIMENTAL DESIGN: Thirty-one human gliomas with
different grades of malignancy were investigated for Egr-1 mRNA and the
protein expression, frequency, and spectrum of p53 gene mutations, mdm2
gene amplification, and p16/INK4a/ARF allele loss. RESULTS: The
amplification of Mdm2 and the deletion of the p16/INK4a gene was found
in 3 and 5 cases, respectively, whereas mutations of p53, including two
novel mutations, were observed in 10 other cases. The three types of
changes occurred strictly mutually exclusively, emphasizing that these
genes operate in a common pathway critical to glioma progression. EGR-1
mRNA was significantly down-regulated in astrocytomas (14.7 +/- 5.1%)
and in glioblastomas (33.6 +/- 10.0%) versus normal brain. Overall,
EGR-1 mRNA was strongly suppressed (average, 15.2 +/- 13.9%) in 27 of 31
cases (87%), independent of changes in p16/INK4a/ARF and Mdm2; whereas 4
of 31 cases with residual EGR-1 expression as well as the highest EGR-1
variance segregated with p53 mutations. Immunohistochemical analyses
confirmed the suppression of EGR-1 protein. CONCLUSIONS: These results
indicate that EGR-1 is commonly suppressed in gliomas independent of
p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors
bearing p53 mutations, and these results implicate an EGR-1 growth
regulatory mechanism as a target of inactivation during tumor
progression.
11
UI - 11782684
AU - Grzesiakowska U; Tacikowska M
TI -
An assessment of the effectiveness of magnetic resonance imaging in
delayed sequences after administration of Gd-DTPA contrast in the
detection of metastatic lesions in the brain.
SO - Med Sci Monit 2002 Jan;8(1):MT21-4
AD - Department of Radiology, Institute of Oncology, Warsaw, Poland.
BACKGROUND: Advances in oncology in recent years have made it possible
to undertake radical interventions even in advanced cases. Local
treatment, surgical or radiosurgical, is applied ever more frequently in
cases of metastases to the brain. This requires accurate determination
of the number and location of metastases by means of imaging techniques.
The goal of our research was to establish whether the use of sequences
delayed by 20-30 minutes after gadolinium injection improves the number
of metastatic lesions detected in the brain by MRI. MATERIAL/METHODS:
Twenty-eight patients were studied, ranging in age from 24 to 72 years,
diagnosed with malignant tumors and suspected metastases to the brain.
MRI examinations were performed with a 2T unit in SE T1 immediately
after i.v. administration of a 0.1 mmol/kg dose of gadolinium, and again
20-30 minutes after contrast injection; both sequences were done in
axial projection in layers identical as in the SE T1 sequence made
before gadolinium injection. The focal lesions were counted and
classified by size. The number of detected lesions was calculated in
each group, comparing early and late phases after contrast injection.
RESULTS: The number of all nodules found in the delayed sequences was
significantly higher in comparison to the early phase after gadolinium
injection. CONCLUSIONS: Delayed sequence should be used to supplement
basic sequences in the diagnosis of malignant metastases to the brain in
selected oncological cases.
12
UI - 11920474
AU - Martini F; Lazzarin L; Iaccheri L; Vignocchi B; Finocchiaro G; Magnani
TI -
I; Serra M; Scotlandi K; Barbanti-Brodano G; Tognon M
Different simian virus 40 genomic regions and sequences homologous with
SV40 large T antigen in DNA of human brain and bone tumors and of
leukocytes from blood donors.
SO - Cancer 2002 Feb 15;94(4):1037-48
AD - Department of Morphology and Embryology, Section of Histology and
Embryology, University of Ferrara, Ferrara, Italy.
BACKGROUND: Many studies found only a small fragment of the large
T-antigen coding sequences in human tumors, raising doubts on
authenticity of SV40 sequences detected in these samples. METHODS: Five
different regions of SV40 DNA were investigated in 106 fresh human tumor
biopsies (25 brain, 69 bone, 12 Wilms' tumors), 71 tumor-derived cell
cultures (38 from brain and 33 from bone tumors) and normal tissues (5
fresh bone biopsies and 38 buffy coats) by polymerase chain reaction
(PCR) techniques and filter hybridization with specific oligoprobes.
Expression of SV40 Tag sequences was analyzed in human tumor specimens
by RT-PCR. RESULTS: SV40 large T-antigen sequences were detected at high
prevalence, in human biopsies of primary brain (37-44%) and bone
(21-37%) tumors, in cell cultures derived from brain (30-54%) and bone
(53-80%) tumors. SV40 Tag sequences were detected in 29% of buffy coats
of blood donors. However, only four brain tumor cell lines showed all
the five regions of the SV40 genome investigated. Expression of SV40 Tag
sequences was found in 11 of 27 (41%) human tumor samples. DNA sequence
analysis indicated that the PCR-amplified products belong to the SV40
wild type. Polymerase chain reaction products of Tag middle portion from
20 of 78 (26%) samples showed a 97% homology with telomeric sequences of
human chromosomes 10 and 11. CONCLUSIONS: Authentic SV40 sequences were
detected in human samples. The expression of SV40 Tag sequences
indicates that SV40 could play a role, as a cofactor, in the
onset/progression of specific human cancers. The inability to detect
some regions of the virus genome may suggest that those regions are not
required for tumor persistence or growth and have been lost or,
alternatively, may be the result of assay conditions that were unable to
PCR-amplify those regions in the tumors. Copyright 2002 American Cancer
Society. DOI 10.1002/cncr.10272
13
UI - 11699553
AU - Reis RM; Hara A; Kleihues P; Ohgaki H
TI -
Genetic evidence of the neoplastic nature of gemistocytes in
astrocytomas.
SO - Acta Neuropathol (Berl) 2001 Nov;102(5):422-5
AD - Unit of Molecular Pathology, International Agency for Research on Cancer
(IARC), Lyon, France.
Gemistocytic astrocytoma is characterized by a predominance of large
astrocytes with plump processes and massive accumulation of glial
fibrillary acidic protein (gemistocytes). This histological variant of
low-grade diffuse astrocytoma (WHO grade II) is prone to more rapid
progression to anaplastic astrocytoma and glioblastoma than the ordinary
fibrillary astrocytoma. The biological basis of this unfavorable
prognosis is unclear, since gemistocytes themselves have low
proliferative activity, even if present in anaplastic astrocytomas or
glioblastomas. This has raised the question of whether gemistocytes are
neoplastic cells or dysplastic reactive astrocytes. In this study,
gemistocytes and non-gemistocytic neoplastic cells were separated by
laser-assisted microdissection from six gemistocytic astrocytomas
carrying TP53 mutations. In all cases, identical TP53 mutations were
identified in both cell types, indicating that gemistocytes are indeed
neoplastic cells. Their lack of proliferative activity may indicate
terminal differentiation.
14
UI - 11886354
AU - Nowak DA; Trost HA
TI -
Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma): a
malformation, hamartoma or neoplasm?
SO - Acta Neurol Scand 2002 Mar;105(3):137-45
AD - Department of Neurology, Academic Hospital Munchen - Bogenhausen,
Technical University of Munich, Munich, Germany. Dr.Dennis.Nowak@gmx.de
OBJECTIVES: Dysplastic gangliocytoma (Lhermitte-Duclos disease) is a
rare disorder, characterized by a slowly progressive unilateral tumour
mass of the cerebellar cortex. The fundamental nature of this apparently
benign entity and in particular its pathogenesis remain unknown. The
debate, whether it represents a neoplastic, malformative or
hamartomatous lesion, is still in progress. Lhermitte-Duclos disease was
recently encountered to be part of a multiple hamartoma-neoplasia
complex (Cowden's syndrome). METHODS: The present account gives a review
of the pertinent literature with emphasize on clinical presentation,
radiological findings, surgical procedures, histopathological features
and pathogenetic considerations of dysplastic cerebellar gangliocytoma.
RESULTS: Dysplastic cerebellar gangliocytoma clusters within the third
to fourth decades of life. Cranial nerve palsies, unsteadiness of gait,
ataxia and sudden neurological deterioration as a result of occlusive
hydrocephalus are frequent signs and symptoms. Associations with other
congenital malformations, such as megalencephaly, polydactylia, multiple
haemangioma and skull abnormalities are common. Magnetic resonance
imaging (MRI) is the diagnostic modality of choice and reveals
characteristic non-enhancing gyriform patterns with enlargement of
cerebellar folia. Surgery is the therapeutic procedure generally
performed and complete resection was attempted in the majority of cases.
The histopathological findings of Lhermitte-Duclos disease include
widening of the molecular layer, which is occupied by abnormal ganglion
cells, absence of the Purkinje cell layer and hypertrophy of the granule
cell layer. CONCLUSIONS: Dysplastic gangliocytoma of the cerebellum is
of benign behaviour and its incidence is extremely rare. The disease
should be considered when confronted with a young adult presenting with
clinical signs of progressive mass effect in the posterior fossa. The
lesion is hypointense on T1- and hyperintense on T2-weighted magnetic
resonance images. Recognition of the disease is of particular
importance, as the frequent but under-reported coexistence with Cowden
syndrome, should prompt thorough clinical and apparative investigation
to detect or exclude concomitant malignancies.
15
UI - 11920585
AU - Held-Feindt J; Mentlein R
TI -
CD70/CD27 ligand, a member of the TNF family, is expressed in human
brain tumors.
SO - Int J Cancer 2002 Mar 20;98(3):352-6
AD - Department of Anatomy, University of Kiel, Kiel, Germany.
held-feindt@anat.uni-kiel.de
CD70 (CD27 ligand) has been implicated in proapoptotic signals mediated
by its receptor CD27 in lymphocytes as well as in proliferative effects
induced by reverse signaling in CD70-positive hematopoetic tumor cells.
We were able to show that CD70 is expressed at the mRNA and protein
level in human meningioma cells, glioma cells from solid human gliomas
as well as glioma cell lines and 1 ependynoma. The intensity of CD70
expression varies considerably between different samples from 1 tumor
type. In the U343 glioma cell line, CD70 was preferentially localized in
the cell processes. Thus, our studies identify CD70 as a new marker
molecule in brain tumors that are of nonhematopoetic origin. Copyright
2002 Wiley-Liss, Inc.
16
UI - 11920588
AU - Dong S; Pang JC; Hu J; Zhou LF; Ng HK
TI -
Transcriptional inactivation of TP73 expression in oligodendroglial
tumors.
SO - Int J Cancer 2002 Mar 20;98(3):370-5
AD - Department of Anatomical and Cellular Pathology, Prince of Wales
Hospital, The Chinese University of Hong Kong, Hong Kong.
The TP73 gene, located on chromosome 1p36.3, encodes a product that
shares significant structural homology with the tumor suppressor TP53.
The aim of this study was to investigate whether TP73 is involved in the
development of oligodendroglial tumors, which frequently carry deletions
involving 1p36.3. Semi-quantitative reverse transcription-polymerase
chain reaction was used to determine TP73 transcript levels. Ten of 24
(42%) tumors showed negligible to more than 5-fold reduction in TP73
expression when compared to normal brain level. To identify potential
mechanisms that may modulate TP73 transcription in oligodendroglial
tumors, we performed mutation analysis on the TP73 gene. No somatic
mutations were however detected in the gene sequence. We then evaluated
the possible involvement of epigenetic change in TP73 expression.
Bisulfite genomic sequencing detected aberrant hypermethylation at the
5' region upstream and including the first exon of the TP73 gene in 17
of 44 (39%) oligodendroglial tumors, whereas normal brain tissues showed
no methylation in the same region examined. Moreover, 6 of 10 (60%)
tumors with negligible or decreased levels of TP73 transcripts were
methylation-positive. In conclusion, our results showed that
inactivation of TP73 occurs at the transcriptional level and is
associated with promotor hypermethylation. Loss of or reduced TP73
transcript expression may contribute to the tumorigenesis of
oligodendroglial tumors. Copyright 2002 Wiley-Liss, Inc.
17
UI - 11906512
AU - Valenti MP; Froelich S; Armspach JP; Chenard MP; Dietemann JL; Kerhli P;
TI -
Marescaux C; Hirsch E; Namer IJ
Contribution of SISCOM imaging in the presurgical evaluation of temporal
lobe epilepsy related to dysembryoplastic neuroepithelial tumors.
SO - Epilepsia 2002 Mar;43(3):270-6
AD - Unite d'Explorations Fonctionnelles des Epilepsies, Clinique
Neurologique, Hopitaux Universitaires de Strasbourg, France.
PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are a group of
glioneuronal supratentorial and intracortical lesions often associated
with the early onset of intractable and crippling partial seizures. They
are characterized by their location, multinodular architecture, and
heterogeneous cell composition, with a specific glioneuronal element in
the specific form. Foci of cortical dysplasia may be associated with the
tumoral lesion, and identifying the presence and the extent of cortical
dysplasia is not always easy on magnetic resonance images (MRIs). The
purpose of this article is to evaluate, retrospectively, the usefulness
of ictal single-photon emission computed tomography (SPECT) imaging to
assess the presence and the extent of cortical dysplasia associated with
DNTs in nine patients with intractable temporal lobe epilepsy related to
histopathologically confirmed DNTs. METHODS: The results of the
subtraction of ictal and interictal SPECT coregistered to MRI (SISCOM)
were compared with the results of the examinations of pathological
material after surgery. RESULTS: SISCOM showed a strongly hyperperfused
area corresponding anatomically to electroclinical abnormalities and to
the location of DNTs on MRI. A circumscribed hyperperfusion was present
in DNTs without cortical dysplasia, limited to the location of the tumor
on MRI. In cases of associated cortical dysplasia, a widespread
hyperperfusion including areas corresponding to normal perilesional
regions on MRI was found. CONCLUSIONS: SISCOM, used among presurgical
investigations, contributes to detecting cortical dysplasia associated
with DNTs. Concordance between the symptomatogenic zone (defined from
the medical history and electroclinical data), MRI scans, SISCOM
pattern, and complete resection of the epileptic zone was predictive of
a good postsurgical outcome.
18
UI - 11844241
AU - Uranishi R; Awadallah NA; Ogunshola OO; Awad IA
TI -
Further study of CD31 protein and messenger ribonucleic acid expression
in human cerebral vascular malformations.
SO - Neurosurgery 2002 Jan;50(1):110-5; discussion 115-6
AD - Neurovascular Surgery Program, Department of Neurosurgery, Yale
University Medical School, New Haven, Connecticut, USA.
OBJECTIVE: In a previous study, we documented lower levels of
immunoexpression of platelet endothelial cell (EC) adhesion molecule
(CD31) in paraffin sections of cerebral cavernous malformations (CCMs),
compared with arteriovenous malformations (AVMs) or normal brain tissue.
We hypothesized that down-regulation of CD31 in CCMs might represent a
distinctive phenotypic feature of ECs in this disease. To confirm this
hypothesis, we further examined both protein and messenger ribonucleic
acid (mRNA) expression of CD31, using immunohistochemical and in situ
hybridization analyses, in fresh-frozen specimens of CCMs, AVMs, and
control brain tissue. METHODS: Fresh-frozen sections of four AVMs, five
CCMs, and four control brain tissue specimens obtained from surgical
resections were immunohistochemically stained with antibodies to von
Willebrand factor and two distinct epitopes of CD31. In two AVMs, four
CCMs, and three control brain tissue samples from the aforementioned
group, the expression of CD31 mRNA was also examined by using in situ
hybridization. Large (>100-microm) and small (<100-microm) vessels were
counted and assessed for protein and mRNA expression. RESULTS: In all
tissues, ECs in the majority of vessels were immunopositive for CD31
with two distinct antibodies. CD31 mRNA was expressed in some but not
all vessels in AVMs, CCMs, and control brain tissue. There were no
statistically significant differences in CD31 protein or mRNA expression
in CCMs, AVMs, and control brain tissue. CONCLUSION: The expression of
CD31 in CCMs can be underestimated in paraffin sections. There does not
seem to be a unique phenotypic differentiation of CD31 expression in ECs
of CCMs or AVMs, compared with control brain tissue.
19
UI - 11844270
AU - Yoshizato K; Zapf S; Westphal M; Berens ME; Giese A
TI -
Thromboxane synthase inhibitors induce apoptosis in migration-arrested
glioma cells.
SO - Neurosurgery 2002 Feb;50(2):343-54
AD - Department of Neurosurgery, University Hospital Eppendorf, Hamburg,
Germany.
OBJECTIVE: Because of the wide dissemination of malignant glioma cells
by the time that malignant glioma is diagnosed, anti-invasive strategies
that are designed to limit their further spread may be of little value
unless mechanisms of the invasive cascade can be used to render invasive
cells susceptible to cytoreductive treatments. We recently determined
that elevated thromboxane synthase gene expression and enzymatic
activity are associated with a highly migratory phenotype of glioma
cells in vitro and that specific inhibitors of this enzyme block cell
migration. Interference with this inherent phenotype of malignant
gliomas also affects glioma cell proliferation and apoptosis. METHODS:
To study the effect of thromboxane synthase inhibitors on motility,
metabolic activity, and cell death, we used five human glioma cell
lines, four glioblastoma-derived, low-passage cell cultures, normal
human astrocytes, and fibroblasts. Motility was measured in a monolayer
migration assay. Caspase activation as an early event in apoptotic cell
death was assessed using a caspase 3 cleavage assay. Intracellular
deoxyribonucleic acid (DNA) fragmentation was detected by enzyme-linked
immunosorbent assay quantification of histone-complexed DNA. Subsequent
cell death was scored by trypan blue exclusion. RESULTS: In this study,
we demonstrate that the treatment of human glioma cells with the
specific thromboxane synthase inhibitor furegrelate leads first to
caspase activation (detectable 6 h after treatment), then to DNA
fragmentation (24-48 h after treatment) and subsequent cell death.
Caspase inhibitors abrogate this effect. Furthermore, the inhibition of
thromboxane synthase by furegrelate increases cells' susceptibility to
the induction of DNA fragmentation by camptothecin, etoposide,
N,N'-bis(2-chloroethyl)-N-nitrosourea, and anti-CD95 antibodies. No
induction of apoptosis was observed in normal astrocytes and
fibroblasts. CONCLUSION: These data indicate that thromboxane synthase
may represent a vortex of divergent signaling cascades that regulate
motility and apoptosis in glioma cells. This paradigm may offer a novel
perspective in the treatment of patients with malignant gliomas.
20
UI - 11878219
AU - Golanov AV; Mariashev SA; Korshunov AG; Pronin IN
TI -
[Neurocytoma of the brain]
SO - Zh Vopr Neirokhir Im N N Burdenko 2001 Oct-Dec;(4):36-9
21
UI - 11818186
AU - Tomura N; Kato K; Takahashi S; Sashi R; Izumi J; Narita K; Watarai J
TI -
Multi-shot echo-planar Flair imaging of brain tumors: comparison of
spin-echo T1-weighted, fast spin-echo T2-weighted, and fast spin-echo
Flair imaging.
SO - Comput Med Imaging Graph 2002 Mar-Apr;26(2):65-72
AD - Department of Radiology, Akita University School of Medicine, 1-1-1
Hondo, Akita City, 010-8543, Akita, Japan. tomura@med.akita-u.ac.jp
Multi-shot echo-planar fluid-attenuated inversion-recovery (EPI-Flair)
was compared with spin-echo T1-weighted (SE-T1W), fast SE T2-weighted
(FSE-T2W), and fast Flair (F-Flair) in imaging brain tumors. In 32
patients with various different brain tumors, three reviewers
independently evaluated image quality. Two reviewers evaluated the image
quality of precontrast EPI-Flair to be significantly better than that of
precontrast SE-T1W. Two reviewers evaluated the image quality of
postcontrast EPI-Flair as superior to that of postcontrast SE-T1W.
Artifacts on postcontrast EPI-Flair were significantly more prominent
than those on postcontrast F-Flair. Multi-shot EPI-Flair appeared to be
superior to SE-T1W, and almost equivalent to FSE-T2W in terms of image
quality.
22
UI - 11822983
AU - Pollack IF; Biegel J; Yates A; Hamilton R; Finkelstein S
TI -
Risk assignment in childhood brain tumors: the emerging role of
molecular and biologic classification.
SO - Curr Oncol Rep 2002 Mar;4(2):114-22
AD - Department of Neurosurgery, Children"s Hospital of Pittsburgh, Main
Tower, Floor 3, Room 3705, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
pollaci@chplink@chp.edu
Brain tumors as a group are the most common solid tumors of childhood
and currently have the highest mortality rate. A major emphasis has
historically been placed on stratifying therapy for these tumors based
on histologic and clinical prognostic factors. However, with the
increasing application of molecular approaches to refine the
categorization of these tumors, it has become apparent that
histologically comparable lesions may exhibit diverse patterns of gene
expression and genomic alterations, which may correspond with important
prognostic distinctions. This paper summarizes these observations and
discusses how they are being applied in a preliminary fashion as a
foundation for risk-adapted stratification of childhood brain tumor
therapy.
23
UI - 1855178
AU - Tsanaclis AM; Brem SS; Gately S; Schipper HM; Wang E
TI -
Statin immunolocalization in human brain tumors. Detection of noncycling
cells using a novel marker of cell quiescence.
SO - Cancer 1991 Aug 15;68(4):786-92
AD - Bloomfield Center for Research in Aging, Sir Mortimer B. Davis-Jewish
General Hospital, Ottawa, Ontario, Canada.
Surgical specimens of 35 human brain tumors were examined with a novel
monoclonal antibody, S-44, immunoreactive to statin, a nuclear protein
specifically expressed in quiescent (noncycling) G0-phase cells. Benign
tumors typically were statin positive with labeling indices (LI) between
22% and 96%: acoustic schwannomas (n = 3, mean = 29.9 +/- 19.4%);
meningiomas (n = 4, mean = 59.0 +/- 15.1%); pituitary adenomas (n = 3,
mean = 79.9 +/- 28.2%), and an epidermoid cyst (41.0%). By contrast, the
statin LI of 18 of 24 (75%) malignant brain tumors was less than or
equal to 2%: medulloblastomas (n = 7, mean = 0.3 +/- 0.2%); anaplastic
astrocytomas (n = 3, mean = 1.6 +/- 2.7%); glioblastomas (n = 10, mean =
10.3 +/- 14.4%); metastatic carcinomas (n = 3, mean = 3.0 +/- 4.6); and
a germinoma (0.2%). The vascular endothelium among diverse tumors
typically was statin positive. All 21 tumors with a statin LI less than
10% were malignant, and all nine tumors with a statin LI greater than
40% were benign. The statin LI of benign tumors (n = 11, mean = 55.1 +/-
26.7%) was significantly higher than that of the malignant tumors (n =
24, mean = 5.2 +/- 10.5%, P less than 0.001). The absence of statin
expression is a new way to determine the malignancy of human brain
tumors. The statin LI may be useful to guide the prognosis and treatment
of individual patients. The mechanisms that control statin expression
are important in therapy seeking to shift the proliferating, cycling
cells to the quiescent, G0 compartment.
24
UI - 8930647
AU - Wizigmann-Voos S; Plate KH
TI -
Pathology, genetics and cell biology of hemangioblastomas.
SO - Histol Histopathol 1996 Oct;11(4):1049-61
AD - Neurozentrum der Albert-Ludwigs-Universitat, Abteilung Neuropathologie,
Freiburg, Germany.
Hemangioblastomas are highly vascularized tumors of not well-defined
histological origin which are frequently associated with cysts. They
arise preferentially in cerebellum, medulla and spinal cord and are
histologically indistinguishable from vascular lesions in the retina
(so-called angiomatosis retinae). Hemangioblastomas are the most
frequent manifestations of the von Hippel-Lindau (VHL) disease, an
autosomal-dominant inherited cancer syndrome but also occur as sporadic
non-hereditary tumors. The VHL tumor suppressor gene has recently been
cloned and enormous progress has been made towards the understanding of
molecular biology and biological function of the VHL gene. Germline
mutations in VHL patients, as well as somatic mutations in different
tumors, including hemangioblastomas, have been identified, its ability
to act as a tumor suppressor in vivo has been confirmed, and interaction
with transcription factors Elongin B and C leading to inhibition of
transcriptional elongation has been demonstrated. The mechanism
underlying neovascularization and cyst formation in hemangioblastomas
and how this is linked to inactivation of the VHL tumor suppressor gene
is not known. However, the finding of dramatic up-regulation of vascular
endothelial growth factor (VEGF), a potent endothelial cell growth
factor with vascular permeability-inducing activity, in stromal cells
and the corresponding receptors, VEGFR-1 and VEGFR-2, in tumor
endothelial cells suggests that angiogenesis and cyst formation in
hemangioblastomas may be regulated by this signaling pathway via a
paracrine mechanism.
25
UI - 9067265
AU - Kanno H; Shuin T; Kondo K; Yamamoto I; Ito S; Shinonaga M; Yoshida M;
TI -
Yao M
Somatic mutations of the von Hippel-Lindau tumor suppressor gene and
loss of heterozygosity on chromosome 3p in human glial tumors.
SO - Cancer Res 1997 Mar 15;57(6):1035-8
AD - Department of Neurosurgery, Yokohama City University School of Medicine,
Yokohama, Japan.
Molecular genetic analysis of von Hippel-Lindau tumor suppressor gene
(VHL gene) was performed on 38 tissues of human glial tumors
(ependymoma, 1; astrocytoma, 6; oligodendroglioma, 1; oligoastrocytoma,
2; anaplastic oligoastrocytoma, 3; anaplastic astrocytoma, 14;
glioblastoma multiforme, 11). Somatic DNAs extracted from frozen tumor
specimens were examined by single-strand conformational polymorphism
analysis and direct sequencing. In addition, loss of heterozygosity
(LOH) on chromosome 3p in 15 glial tumor cases, lymphocyte DNAs of which
were available, was examined by use of 10 microsatellite probes and two
polymorphism markers for the VHL gene. Two cases of low-grade gliomas
showed somatic sense mutations in exon 3 of the VHL gene, and 6 of 15
cases (40.0%) showed LOH of chromosome 3p. The VHL gene-mutated cases
also showed LOH. The retention of heterozygosity and high pathological
grade of glial tumors were correlated significantly. In addition,
Kaplan-Meier survival analysis for patients with glial tumors showed
that patients with LOH had a significantly longer survival time than
those without LOH. These results suggest that somatic mutations on 3p,
including the VHL gene, may be involved in tumorigenesis of some
low-grade glial tumors.
26
UI - 9158701
AU - Vortmeyer AO; Gnarra JR; Emmert-Buck MR; Katz D; Linehan WM; Oldfield
TI -
EH; Zhuang Z
von Hippel-Lindau gene deletion detected in the stromal cell component
of a cerebellar hemangioblastoma associated with von Hippel-Lindau
disease.
SO - Hum Pathol 1997 May;28(5):540-3
AD - Laboratory of Pathology and Surgery Branch, National Cancer Institute,
Bethesda, MD 20892, USA.
Central nervous system hemangioblastoma is a neoplasm with
characteristic and well-described histopathological features, including
proliferation of vascular and stromal cells. yet, the histogenesis of
the stromal cell component and its neoplastic capacity as compared with
the vascular component are still controversial. Stromal cells were
selectively procured from formalin-fixed, paraffin-embedded archival
tissue from a von Hippel-Lindau (VHL) disease patient with a cerebellar
hemangioblastoma and studied for loss of heterozygosity (LOH) of the VHL
gene locus and associated microsatellite regions. The stromal cells
consistently showed LOH. Analysis of mixed stromal anti vascular areas
of this tumor and four other hemangioblastomas of VHL patients showed
that loss of heterozygosity was partially obscured. These preliminary
results suggest that the stromal component of hemangioblastomas contains
genetic alterations consistent with
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