National Cancer Institute®
Last Modified: August 1, 2002
UI - 11837537
AU - Uematsu Y; Fujita K; Tanaka Y; Shimizu M; Oobayashi S; Itakura T; Kubo K
TI - Gamma knife radiosurgery for neuroepithelial tumors: radiological and histological changes.
SO - Neuropathology 2001 Dec;21(4):298-306
AD - Department of Neurological Surgery, Wakayama Medical University, Wakayama City, Japan. firstname.lastname@example.org
Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain tumors. However, the effects of RS for neuroepithelial tumors are still obscure. The present study investigates the radiological and histological changes after RS to elucidate the biological effect. There were seven cases (two males and five females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were located in the brainstem, another two in the cerebellum, and one each in the thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy. All cases were evaluated radiologically on MRI before and after RS. Four cases (3 astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were reoperated. These cases were examined using HE and immunohistochemical studies with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on the sections before and after RS. MRI demonstrated perifocal edema and intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting radionecrosis in most of the cases within 6 months after RS. In the central part of the RS, destructive changes were observed in the tumor cells and endothelial cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls were revealed. In the peripheral part, however, some tumors contained viable tumor cells intermingled with blood vessels showing endothelial and pericytic proliferations. The increase of MIB-1 staining index was found in only one case. The p21 immunoreactivity was increased in endothelial cells, although the p53 immunoreactivity was unchanged. These results suggested that radionecrosis occurred earlier and more frequently in neuroepithelial tumors after RS than after conventional radiation.
UI - 12107116
AU - Mueller W; Hartmann C; Hoffmann A; Lanksch W; Kiwit J; Tonn J; Veelken
TI - J; Schramm J; Weller M; Wiestler OD; Louis DN; von Deimling A Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets.
SO - Am J Pathol 2002 Jul;161(1):313-9
AD - Department of Neuropathology, Charite, Humboldt University, Berlin, Germany.
Oligoastrocytomas are heterogeneous tumors that have molecular features that overlap with either oligodendrogliomas or astrocytomas. Differences in the frequency of chromosomal losses of 1p and 19q in oligodendrogliomas are related to tumor location, with a low rate of allelic loss in tumors of the temporal and a high rate in tumors of the frontal, parietal, and occipital lobes. To test the possibility of regional molecular heterogeneity in oligoastrocytoma, we examined a series of 203 gliomas including 68 oligoastrocytomas and two control groups of 73 oligodendrogliomas and 62 astrocytomas for allelic losses of chromosomal arms 1p and 19q, and TP53 mutations, and compared these data with tumor localization. Common molecular alterations were found in oligodendrogliomas and oligoastrocytomas arising in extratemporal sites. In respect to the molecular parameters analyzed, temporal oligoastrocytomas were either indistinguishable from astrocytoma or similar to temporal oligodendrogliomas. Oligodendroglial neoplasms can thus be separated into three molecular subsets, two of which include lesions with the morphological features of oligodendrogliomas and oligoastrocytomas and one resembling temporal oligoastrocytoma. Molecular subclassification thus unifies previous findings about prognosis, behavior, response to therapy, genotype, and location in oligodendroglial tumors.
UI - 11922700
AU - Nishio S; Morioka T; Suzuki S; Fukui M
TI - Tumours around the foramen of Monro: clinical and neuroimaging features and their differential diagnosis.
SO - J Clin Neurosci 2002 Mar;9(2):137-41
AD - Department of Neurosurgery, Kyushu University Hospital, Fukuoka, Japan. email@example.com
The clinical and neuroimaging features of 20 patients with lateral ventricular tumours located around the foramen of Monro were reviewed retrospectively with special emphasis on the differential diagnoses. Histologic types were: eight neurocytomas, four subependymal giant cell astrocytomas (SGCAs), three subependymomas, two fibrillary astrocytomas, and one each of pilocytic astrocytoma, malignant astrocytoma and malignant teratoma. The mean age of the patients with neurocytoma was 29.6 years, with SGCA 13.3 years and with subependymoma 55.3 years. All tumours appeared nodular in shape, and on computed tomography (CT) neurocytomas were either isodense or highdense with the brain, while all subependymomas and SGCAs were lowdense. Calcification was observed in two SGCAs, and one neurocytoma. Five neurocytomas and all four SGCAs showed mild to moderate contrast enhancement, while all three subependymomas showed either no, or scarce, enhancement. Magnetic resonance imaging (MRI) studies were available in 10 patients, with the signal characteristics of four neurocytomas and three SGCAs being nonspecific, while two subependymomas were both hypointense on T1-weighted images and hyperintense on T2-weighted images. Thus important features for differential diagnosis included age of the patient and density on precontrast CT. In this series, either an extensive excision of the tumour or a partial removal, thus relieving the obstruction of the foramina of Monro, usually provided long term survival, with 18 patients surviving a mean of 10.8 years. Copyright 2002, Elsevier Science Ltd. All rights reserved.
UI - 12007145
AU - Vandeputte DA; Troost D; Leenstra S; Ijlst-Keizers H; Ramkema M; Bosch
TI - DA; Baas F; Das NK; Aronica E Expression and distribution of id helix-loop-helix proteins in human astrocytic tumors.
SO - Glia 2002 Jun;38(4):329-38
AD - Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
The Id family of helix-loop-helix proteins is involved in a variety of processes, such as development, proliferation, and angiogenesis. In this study, we investigated the expression pattern of Id1, Id2, and Id3 in surgical specimens of human glial tumors. Western blot analysis demonstrated that all three Id proteins were expressed in astrocytic tumors. Expression levels in high-grade tumors were higher than in low-grade tumors. Immunohistochemical analysis confirmed that many of the tumor astrocytes exhibited strong Id1-3 IR. In contrast, in adult human normal brain, Id expression was low both in resting astrocytes and in endothelial cells. In tumor cells, Id proteins displayed cytoplasmic as well as nuclear localization. Id1-3 IR scores in tumor cells were positively correlated with proliferation indices. Moreover, Id1-3 IR was detected in endothelial cells of the astrocytic tumor blood vessels. The vascular Id1-3 expression correlated positively with tumor vascularity and grade. These results support the role of the Id gene family in the enhanced proliferative potential of tumor astrocytes. The evidence also supports the involvement of the Id gene family in tumor angiogenesis, a process that critically influences the malignant behavior of glial tumors. Copyright 2002 Wiley-Liss, Inc.
UI - 12125736
AU - Blumcke I; Wiestler OD
TI - Gangliogliomas: an intriguing tumor entity associated with focal epilepsies.
SO - J Neuropathol Exp Neurol 2002 Jul;61(7):575-84
AD - Department of Neuropathology, University of Erlangen, Germany.
Gangliogliomas represent the most frequent tumor entity in young patients suffering from chronic focal epilepsies. In a series of 326 gangliogliomas collected from the University of Bonn Epilepsy Surgery Program and other departments of neuropathology in Germany, Austria, and Switzerland, epidemiological findings and histopathological hallmarks of gangliogliomas are systematically reviewed. The majority of these tumors occur within the temporal lobe and reveal a biphasic histological architecture characterized by a combination of dysplastic neurons and neoplastic glial cell elements. However, gangliogliomas exhibit a considerable variability in their histopathological appearance. Immunohistochemical studies are an important tool to discriminate these neoplasms from other tumor entities. Almost 80% of gangliogliomas reveal immunoreactivity for CD34, a stem cell epitope not expressed in normal brain. Immunohistochemical reactions for MAP2 or NeuN can be employed to characterize the dysplastic nature of neurons in those areas difficult to discriminate from pre-existing brain parenchyma. Less than 50% of the cases display binucleated neurons. With the frequent finding of "satellite" tumor clusters in adjacent brain regions, gangliogliomas are microscopically less circumscribed than previously assumed. The distinction from diffusely infiltrating gliomas is of considerable importance since tumor recurrence or malignant progression are rare events in gangliogliomas. Only little is known about the molecular pathogenesis of these glioneuronal tumors. Our findings support a dysontogenic origin from a glioneuronal precursor lesion with neoplastic, clonal proliferation of the glial cell population. Candidate genes appear to associate with neurodevelopmental signaling cascades rather than cell cycle control or DNA repair mechanisms. The reelin signaling and tuberin/insulin growth receptor pathways have recently been implicated in ganglioglioma development. Powerful new molecular genetic and biological tools can now be employed to unravel the pathogenesis of these intriguing lesions.
UI - 12057797
AU - Jaing TH; Wang HS; Hung IJ; Tseng CK; Yang CP; Hung PC; Lui TN
TI - Intracranial germ cell tumors: a retrospective study of 44 children.
SO - Pediatr Neurol 2002 May;26(5):369-73
AD - Division of Hematology, Chang Gung Children's Hospital, Taoyuan, Taiwan.
This 16-year retrospective study review sought to determine the factors influencing prognosis and treatment results of all patients with primary intracranial germ cell tumors treated at our hospital who were younger than 17 years of age at the time of diagnosis. A total of 44 patients were treated during the study period, including 32 males and 12 females with a male:female ratio of 2.67:1. The median age at diagnosis was 12 years and 5 months of age (range = 2-16 years). The 44 intracranial germ cell tumors consisted of 27 pure germinomas (61.4%) and 17 nongerminomatous germ cell tumors, including 10 mixed germ cell tumors (22.7%), three yolk sac tumors (7.8%), two immature teratomas (4.5%), and two choriocarcinomas (4.5%). Univariate analysis of prognostic factors using Kaplan-Meier survival estimates revealed that only histologic tumor type was correlated with outcome (P < 0.005). The projected 5-year overall survival and event-free survival rate of patients with germinomas vs those with intracranial germ cell tumors were 92.6%, 92.6% vs 47.3%, and 42.1%, respectively. Our analysis suggests that radiation involving the spinal axis has limited usefulness in patients with intracranial germ cell tumor, although better results have been obtained for germinomas using radiotherapy in this study.
UI - 12115571
AU - Filippini G; Maisonneuve P; McCredie M; Peris-Bonet R; Modan B;
TI - Preston-Martin S; Mueller BA; Holly EA; Cordier S; Choi NW; Little J; Arslan A; Boyle P Relation of childhood brain tumors to exposure of parents and children to tobacco smoke: the SEARCH international case-control study. Surveillance of Environmental Aspects Related to Cancer in Humans.
SO - Int J Cancer 2002 Jul 10;100(2):206-13
AD - Neuroepidemiology Research Unit, Istituto Nazionale Neurologico C Besta, Milan, Italy. firstname.lastname@example.org
The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case-control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0-19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population-based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the child's age at diagnosis, the histologic type of tumor or center. Copyright 2002 Wiley-Liss, Inc.
UI - 12097291
AU - Rood BR; Zhang H; Weitman DM; Cogen PH
TI - Hypermethylation of HIC-1 and 17p allelic loss in medulloblastoma.
SO - Cancer Res 2002 Jul 1;62(13):3794-7
AD - Department of Pediatric Hematology/Oncology, Children's Research Institute, Children's National Medical Center, Washington, DC. 20010, USA.
Medulloblastoma is the most common malignant brain tumor in children.Chromosome arm 17p13.3 is reduced to homozygosity in 35-50% of medulloblastomas,making it the most frequent genetic alteration in these tumors. HIC-1 (hypermethylated in cancer) is a putative tumor suppressor gene located in the area of common deletion. HIC-1 resides in a CpG island and is hypermethylated in many different tumor types. Therefore, we studied a series of tumor specimens for hypermethylation and deletion of the region containing the HIC-1 gene to determine whether these two mechanisms of gene inactivation play a complimentary role in medulloblastoma. Southern blotting was performed using the methylation-sensitive restriction endonuclease NotI. Methylation of NotI restriction sites located in HIC-1 was demonstrated in 26 (72%) of 36 tumors and 11 (92%) of 12 specimens of normal brain. Of these 26 tumors, 23 differed significantly from normal brain. A greater proportion of the cells from the tumors showed methylated alleles of the HIC-1 gene. A group of 15 (42%) of 36 tumors exhibited loss of heterozygosity (LOH) for DNA sequences located on chromosome arm 17p. There was no significant correlation between LOH and methylation status (P = 0.19). Methylation in tumors beyond that seen in normal brain predicted poor overall survival independent of clinical risk category (P = 0.014). The results of our study show that methylation of the CpG island that contains the HIC-1 gene is common in medulloblastoma and, together with LOH of 17p, may be a critical event in the formation and aggressiveness of this tumor.
UI - 12097292
AU - Paunu N; Lahermo P; Onkamo P; Ollikainen V; Rantala I; Helen P; Simola
TI - KO; Kere J; Haapasalo H A novel low-penetrance locus for familial glioma at 15q23-q26.3.
SO - Cancer Res 2002 Jul 1;62(13):3798-802
AD - Department of Pathology, Tampere University Hospital, FIN-33521 Tampere, Finland. email@example.com
Epidemiological studies and case reports suggest that familial clustering of gliomas may occur in families that do not fit any known tumor syndromes. In the present study, 15 familial glioma pedigrees from a limited geographical area were hypothesized to carry the same low-penetrance susceptibility allele. We used a two-stage strategy for disease gene mapping. A genome scan in four glioma families revealed four interesting loci at chromosome arms 1q, 6q, 8p, and 15q. Additional markers in these regions provided evidence of significant linkage to 15q23-q26.3 with a maximum nonparametric linkage score of 3.35 with marker D15S130. Investigation of all 15 glioma families by association analysis (haplotype pattern mining) and through use of the transmission/disequilibrium test gave further evidence of significant association/transmission distortion at the same 15q locus (P = 0.02 and P = 0.03, respectively). No evidence of involvement of known tumor syndromes was obtained from the data provided by the linkage analysis or hospital records. Thus, the first genome-wide linkage analysis of familial glioma suggests a novel susceptibility locus at 15q23-q26.3.
UI - 12124842
AU - Pelc K; Vincent S; Ruchoux MM; Kiss R; Pochet R; Sariban E; Decaestecker
TI - C; Heizmann CW Calbindin-d(28k): a marker of recurrence for medulloblastomas.
SO - Cancer 2002 Jul 15;95(2):410-9
AD - Department of Pediatrics, Hopital des Enfants, Brussels, Belgium.
BACKGROUND: The expression of the Ca(2+)-binding protein calbindin-D(28k) was analyzed in medulloblastomas in relation to clinical features and other biologic markers related to cell proliferation, differentiation, p53, and cerebellar developmental regulated gene expression. METHODS: Immunohistochemistry was carried out on histologic slides from a first retrospective series of 29 nonmetastatic and 10 metastatic medulloblastoma formalin-fixed, paraffin-embedded tissues, using specific antibodies against calbindin-D(28k), calretinin, alpha-parvalbumin and beta-parvalbumin, and S100 proteins. Informed consent was obtained from the subjects and/or guardians. Other biologic markers for differentiation, cell proliferation, the expression of the p53 tumor suppressor gene protein, and cerebellar developmental regulated genes were similarly investigated. A second series of 16 medulloblastomas from young patients (younger than 15 years) was added in order to validate the results obtained in the first series. RESULTS: Of all the markers investigated, only calbindin-D(28k) was significantly associated with prognosis. Survival and remission (i.e. recurrence free) time analysis performed on all the cases (n = 55) confirmed a high risk of death (P = 0.004) and recurrence (P = 0.003) associated with calbindin-positivity. As calbindin-positivity was predominantly observed in tumors from young patients, the authors confirmed its prognostic value in the subgroup of patients younger than 15 years (n = 37). Cox regression analysis showed a significant and independent prognostic value for calbindin expression and, to a lesser extent, the type of surgery (total or subtotal). Three risk groups were thus identified, distinguishing among the cases characterized by a total resection and calbindin-negativity (good prognosis), by a subtotal resection and calbindin-negativity (intermediary), and by calbindin-positivity (bad prognosis). CONCLUSIONS: The current study suggests that calbindin-positive medulloblastomas represent a subclass of aggressive tumors more frequently seen in younger patients. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10666
UI - 12127399
AU - Koschny R; Koschny T; Froster UG; Krupp W; Zuber MA
TI - Comparative genomic hybridization in glioma: a meta-analysis of 509 cases.
SO - Cancer Genet Cytogenet 2002 Jun;135(2):147-59
AD - Institute of Human Genetics, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany.
Much data about genetic imbalances in tumors have been accumulated by comparative genomic hybridization (CGH). In order to distinguish between significantly and coincidentally involved regions in glioma by means of a meta-analysis, we summarized and analyzed the CGH results of 509 cases published in 26 reports between 1992 and 2001. The expansion of all aberrations to the 850-band level impressively visualized distinct patterns in astrocytoma, oligodendroglioma, and ependymoma as well as loci of frequent aberrations. For example, in astrocytoma the frequency of gains culminated at 7p12, 8q24.1, and 12q13-q15 (the loci of EGF-R, C-MYC and CDK4, respectively) and losses at 9p21 (the locus of p15 and p16) and 10q23.3 where PTEN resides. Most chromosomes were variably prone to copy number changes at different scales of aberrations. At the whole chromosome level the analysis showed +7, -10 in astrocytoma and +9, +18 in ependymoma, but +20q, -9p in astrocytoma and +1q, -22q in ependymoma at the p-q arm level. Furthermore, we could confirm the correlation between the average number of copy alterations per patient (average number of copy alterations [ANCA] index) and malignancy for astrocytoma in a refined graduation as well as for oligodendroglioma. As a new parameter, the average number of affected GTG-bands per patient (average number of affected GTG bands [ANAG] index) showed an even more striking correlation with the World Health Organization grade for gains and losses.
UI - 1510081
AU - Modan B; Wagener DK; Feldman JJ; Rosenberg HM; Feinleib M
TI - Increased mortality from brain tumors: a combined outcome of diagnostic technology and change of attitude toward the elderly.
SO - Am J Epidemiol 1992 Jun 15;135(12):1349-57
AD - National Center for Health Statistics, Centers for Disease Control, Hyattsville, MD 20782.
United States national data were used to assess factors responsible for the increase of brain tumor mortality. Between 1968 and 1988, death rates increased 50% among those aged 65-74 years, 200% among those aged 75-84 years, and 800% in the oldest old. Rate of increase and maximum death rate have changed over time. Death rate among the population aged 65-74 years peaked in the mid-1980s, while among those aged 85 years and older it is projected to continue increasing throughout the 1990s. The patterns of rate increases were almost identical in the two sexes, as well as among whites and nonwhites. There was a strong correlation over time of death rates with head diagnostic procedures (r = 0.96) and with the pace of computerized axial tomography installation (r = 0.91). The authors conclude that the reported increase in brain tumor mortality is not genuine, but represents a combination of three factors: availability of more sophisticated, noninvasive diagnostic technology; change in the attitude toward care of the elderly; and introduction of support programs such as Medicare that facilitate diagnostic procedures in the elderly.
UI - 7998596
AU - Polednak AP
TI - Re: "Increased mortality from brain tumors: a combined outcome of diagnostic technology and change of attitude toward the elderly".
SO - Am J Epidemiol 1994 Dec 15;140(12):1138-43
UI - 8546112
AU - Gurney JG; Mueller BA; Davis S; Schwartz SM; Stevens RG; Kopecky KJ
TI - Childhood brain tumor occurrence in relation to residential power line configurations, electric heating sources, and electric appliance use.
SO - Am J Epidemiol 1996 Jan 15;143(2):120-8
AD - Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA.
To assess the relation between childhood brain tumor occurrence and exposure to potential sources of residential magnetic fields, a population-based case-control study of incident brain tumors was conducted in the Seattle, Washington, area at the Fred Hutchinson Cancer Research Center from 1989 to 1994 among children younger than age 20 years who were diagnosed from 1984 to 1990. The specific aims were to evaluate whether proximity to high-current residential power lines, as defined by the Wertheimer-Leeper code, or use of electric appliances or electric heating sources by the mother while pregnant or by the child before diagnosis were associated with increased risks of brain tumor occurrence. The mothers of 133 cases and 270 controls (recruited by random digit dialing) participated. Risk of brain tumor occurrence did not increase with increasing exposure, as indicated by the five-level Wertheimer-Leeper code. When exposure was dichotomized as high versus low, the odds ratio was 0.9 (95% confidence interval 0.5-1.5) and did not vary significantly by sex, age, or histology. No elevations in risk were found for ever versus never use of electric blankets, water beds, or electric heating sources. Odds ratios were slightly elevated for nine appliances and were at or below 1.0 for eight others. These data do not support the hypothesis that exposure to magnetic fields from high-current power lines, electric heating sources, or electric appliances is associated with the subsequent occurrence of brain tumors in children.
UI - 8546113
AU - Poole C
TI - Invited commentary: evolution of epidemiologic evidence on magnetic fields and childhood cancers.
SO - Am J Epidemiol 1996 Jan 15;143(2):129-32; discussion 133-6
AD - Department of Epidemiology and Biostatistics, Boston University School of Public Health, MA, USA.
UI - 12122877
AU - Fazekas I; Kerekes E; Hegedus B; Nyary I
TI - Identification of gliomas by morphological and immunocytochemical analysis in cell cultures.
SO - Ideggyogy Sz 2002 May 20;55(5-6):173-9
AD - National Institute of Neurosurgery, Budapest.
INTRODUCTION: The morphology and immunocytochemical properties of 250 different monolayer cultures derived from various human brain tumor specimens were investigated on purpose to support and complement the neuropathological diagnosis. In this study analyses of 124 glioma cases are presented. METHODS: The tumor samples were mechanically dissociated and seeded on glass coverslips. After the formation of the monolayer cultures were fixed and stained by May-Grunwald-Giemsa method for the morphological examination. Semi-quantitative immunocytochemical labeling included several different types of mono- and polyclonal primary antibodies using avidin-biotin visualization system. In nine cases of the glioblastomas the sufficient proliferation made possible to establish cell lines from the primary cultures. RESULTS: The glial origin of the tumors was identified in 124 cases based upon the presence of glial fibrillary acidic protein. A negative correlation between the intensity of glial fibrillary acidic protein immunostaining and the grade of tumor malignancy was found. During long-term cultivation of the higher grade gliomas the incidence and intensity of glial fibrillary acidic protein labeled cells was decreasing. Both the vimentin and the neuron specific enolase labeling were in general stronger than the glial fibrillary acidic protein and almost all the cells were stained. The incidence of Ki-67 positive cells increased with the grade of malignancy. Concerning the tumor classification our immunocytochemical results correlated with the routine histopathological examination. CONCLUSIONS: On the basis of these results we conclude that monolayer cultures obtained from tumor specimens can support and complement the correct diagnosis of the various human brain tumors.
UI - 12084346
AU - Kim JY; Koralnik IJ; LeFave M; Segal RA; Pfister LA; Pomeroy SL
TI - Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequences.
SO - Neuro-oncol 2002 Jul;4(3):165-70
AD - Division of Neuroscience, Department of Neurology, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
To address the hypothesis that medulloblastoma or supratentorial primitive neuroectodermal tumor (sPNET) can arise through infection by polyomaviruses, we examined genomic DNA isolated from 15 primary medulloblastoma and 5 sPNET biopsy specimens and from 2 medulloblastoma cell lines for the presence of DNA sequences from the polyomaviruses simian virus 40 (SV40), JC virus, and BK virus. These polyomaviruses have oncogenic potential in animals, and their DNA sequences have been detected in other surveys of various solid tumors, including childhood brain tumors. The tumor DNA samples were analyzed by Southern blot hybridization of polymerase chain reaction products that employed probes designed to detect specific polyomavirus sequences. Neither JC virus nor BK virus DNA sequences were detected in any of the specimens. None of the primary medulloblastoma or sPNET specimens contained SV40 sequences. However, SV40 DNA coding and noncoding sequences were detected in the D283-Med (medulloblastoma) cell line. Immunocytochemical studies of D283-Med revealed nuclear expression of SV40 large T antigen. In contrast to childhood ependymomas and choroid plexus tumors, medulloblastomas and sPNETs infrequently express evidence of polyomavirus infection.
UI - 12084348
AU - Kuriyama H; Lamborn KR; O'Fallon JR; Iturria N; Sebo T; Schaefer PL;
TI - Scheithauer BW; Buckner JC; Kuriyama N; Jenkins RB; Israel MA Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas.
SO - Neuro-oncol 2002 Jul;4(3):179-86
AD - The Preuss Laboratory for Molecular Neuro-Oncology, Brain Tumor Research Center, University of California-San Francisco, San Francisco, CA 94143, USA.
We evaluated the association of spontaneous apoptosis and an apoptosis/proliferation index with survival to determine the potential of such measures to serve as predictive markers for patients with glioblastoma multiforme (GBM). We examined the extent of spontaneous apoptosis in tumors from newly diagnosed patients, 75 with GBM and 21 with anaplastic astrocytoma, who were entered on treatment protocols of the North Central Cancer Treatment Group. In the group of GBM patients, those with a higher apoptotic index tended to live longer ( P = 0.04; Cox proportional hazards model including performance score, age, and extent of resection in a multivariate model). We found that the apoptotic index values for anaplastic astrocytoma patients tended to be lower than those in the GBM patients, although with small sample sizes, the result was not statistically significant ( P = 0.1). We also examined expression of the Ki-67 cell proliferation antigen immunohistochemically using the MIB-1 monoclonal antibody. Ki-67 expression did not provide additional information regarding the survival of patients with GBM. In this group of GBM patients, those patients with higher apoptotic index/proliferation ratios had a better prognosis than did those with a low ratio ( P < 0.021, same model as above). These findings suggest that both apoptosis and a cell death/cell proliferation ratio are associated with patient survival, and they may be useful for either the clinical evaluation of patients with GBM or the stratification of patients for treatment evaluation.
UI - 12068298
AU - Taylor MD; Liu L; Raffel C; Hui CC; Mainprize TG; Zhang X; Agatep R;
TI - Chiappa S; Gao L; Lowrance A; Hao A; Goldstein AM; Stavrou T; Scherer SW; Dura WT; Wainwright B; Squire JA; Rutka JT; Hogg D Mutations in SUFU predispose to medulloblastoma.
SO - Nat Genet 2002 Jul;31(3):306-10
AD - Division of Neurosurgery, The Arthur and Sonia Labatt Brain Tumour Research Centre, Toronto, Canada.
The sonic hedgehog (SHH) signaling pathway directs the embryonic development of diverse organisms and is disrupted in a variety of malignancies. Pathway activation is triggered by binding of hedgehog proteins to the multipass Patched-1 (PTCH) receptor, which in the absence of hedgehog suppresses the activity of the seven-pass membrane protein Smoothened (SMOH). De-repression of SMOH culminates in the activation of one or more of the GLI transcription factors that regulate the transcription of downstream targets. Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal-cell carcinomas, medulloblastomas and other cancers (a pattern consistent with nevoid basal-cell carcinoma syndrome, NBCCS). In keeping with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene occur in sporadic basal-cell carcinomas and medulloblastomas. We report here that a subset of children with medulloblastoma carry germline and somatic mutations in SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by loss of heterozygosity of the wildtype allele. Several of these mutations encode truncated proteins that are unable to export the GLI transcription factor from nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a newly identified tumor-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway through a newly identified mechanism.
UI - 12087206
AU - Kim TH; Joh JH; Kim MY; Kim YM; Han KS
TI - Fetal pericallosal lipoma: US and MR findings.
SO - Korean J Radiol 2002 Apr-Jun;3(2):140-3
AD - Department of Radiology, Sejong Heart Institute, Sejong General Hospital, Pucheon, Kyunggido, Korea. firstname.lastname@example.org
We report a case of fetal pericallosal lipoma occurring at the anterior interhemispheric fissure and associated with agenesis of the corpus callosum. During targeted prenatal ultrasonography at 26 weeks' gestation, the lesion was seen as a highly echogenic mass. MR imaging performed at 35 weeks' gestation and during the postnatal period revealed a pericallosal fatty mass and agenesis of the corpus callosum.
UI - 12112531
AU - Actor B; Cobbers JM; Buschges R; Wolter M; Knobbe CB; Reifenberger G;
TI - Weber RG Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components.
SO - Genes Chromosomes Cancer 2002 Aug;34(4):416-27
AD - Abteilung Molekulare Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Gliosarcoma is a variant of glioblastoma multiforme characterized by two components displaying gliomatous or sarcomatous differentiation. We investigated 38 gliosarcomas for aberrations of tumor-suppressor genes and proto-oncogenes that are commonly altered in glioblastomas. Amplification of CDK4, MDM2, EGFR, and PDGFRA were found in 11% (4/35), 8% (3/38), 8% (3/38), and 3% (1/35) of the tumors, respectively. Nine of 38 gliosarcomas (24%) carried TP53 mutations. PTEN mutations were identified in 45% (9/20) of the investigated tumors. Twenty gliosarcomas were analyzed by comparative genomic hybridization (CGH). Chromosomal imbalances commonly detected were gains on chromosomes 7 (15/20; 75%), X (4/20; 20%), 9q, and 20q (3/20, 15% each); and losses on chromosomes 10 and 9p (7/20, 35% each), and 13q (3/20, 15%). Five different high-level amplifications were mapped to 4q12-q21 (1 case), 6p21 (1 case), 7p12 (2 cases), proximal 12q (4 cases), and 14q32 (1 case) by CGH. Southern blot and/or differential PCR analyses identified amplification of PDGFRA (4q12), CCND3 (6p21), EGFR (7p12), CDK4 (12q14) and/or MDM2 (12q14.3-q15), and AKT1 (14q32.3) in the respective tumors. Separate analysis of the gliomatous and sarcomatous components of eight gliosarcomas by CGH after microdissection and universal DNA amplification revealed that both components shared 57% of the chromosomal imbalances detected. Taken together, our data indicate that the genomic changes in gliosarcomas closely resemble those found in glioblastomas. However, the number of chromosomes involved in imbalances in gliosarcomas was significantly lower than that in glioblastomas, indicating a higher genomic stability in gliosarcomas. In addition, we provide further support for the hypothesis that the gliomatous and sarcomatous components are derived from a single precursor cell clone, which progressed into subclones with distinct morphological features during tumor evolution. According to our data, gain/amplification of genes on proximal 12q may facilitate the development of a sarcomatous phenotype. Copyright 2002 Wiley-Liss, Inc.
UI - 12135196
AU - Chuang SS; Lee PS; Lin CN; Tsai TC; Chio CC; Que J; Huang CT
TI - Primary brain lymphoma: a report of eight cases from a medical center in southern Taiwan.
SO - Zhonghua Yi Xue Za Zhi (Taipei) 2002 Apr;65(4):172-9
AD - Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan, ROC.
BACKGROUND: Primary brain lymphoma (PBL) in Taiwan has been reported only in three series with very limited immunophenotypic characterization. METHODS: We retrospectively studied PBL cases with history review, immunohistochemistry, and in situ hybridization (ISH) for Epstein-Barr virus-encoded mRNA (EBER) from a single institution in southern Taiwan during 1989-2000. RESULTS: We found eight cases of PBL including four males and four females with mean age of 64.1 years and median of 63.0. The major presenting symptoms were headache, poor memory, slurred speech, and hemiplegia in three patients each. All patients had stage I solitary tumor. Half of the patients received tumor excision, the other half, stereotactic biopsy. Seven cases were of diffuse large B-cell type (DLBL), with expression of bcl-2 in six cases. They were all negative for CD5, CD10, bcl-6, and EBER. The eighth patient had anaplastic large cell lymphoma (ALCL) of T-cell phenotype with expression of cytotoxic markers and was positive for EBER. Two were lost to follow up. The median follow-up time for the remaining six was 11.2 months (range, 5.5 - 25.0). They all received radiotherapy with initial complete remission. Two died of the disease, another of cardiopulmonary failure, and the other of stroke or recurrence. The remaining two were free of disease for 9.6 and 25.0 months after radiotherapy alone. The 1-year survival rate was 60%. CONCLUSIONS: We have fully characterized eight cases of PBL, including seven DLBLs and one ALCL, in southern Taiwan that occurred in an older age group. Old age, immunophenotype (bcl-2-positivity and bcl-6-negativity), and lack of systemic chemotherapy were probably responsible for the shorter survival as compared to other studies. Radiotherapy seems to be effective for inducing complete remission and even long-term survival in some patients, however, systemic chemotherapy should be administered to prevent recurrence and to achieve long-term survival.
UI - 11855573
AU - Pobereskin LH
TI - The completeness of brain tumour registration in Devon and Cornwall.
SO - Eur J Epidemiol 2001;17(5):413-6
AD - Department of Neurosurgery, Derriford Hospital, Plymouth, UK. email@example.com
OBJECTIVES: To determine ascertainment rates for primary brain tumours and examine factors influencing those rates. DESIGN: Comparison of a clinical database with official figures from the Regional Cancer Intelligence Unit. RESULTS: Of 1480 potential cases 52% appeared in the registry. Only two-thirds of patients operated upon were registered and less than one-third of those who were not operated appeared in the registry. Independent predictors of registration were having had an operation, 5.47 (4.19-7.17) (odds ratio (95% CI)), being over 60 years of age, 1.62 (1.26-2.07), and having a tumour requiring radiotherapy, 2.52 (1.74-3.66). CONCLUSIONS: There is asymmetric registration of primary brain tumours in Devon and Cornwall with under registration of more benign tumours in younger patients. If similar problems exist across the United Kingdom, this could have a negative influence on survival rates, and international comparisons of such rates should be performed with caution.
UI - 12111801
AU - Ray SK; Patel SJ; Welsh CT; Wilford GG; Hogan EL; Banik NL
TI - Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: upregulation of calpain and caspase-3.
SO - J Neurosci Res 2002 Jul 15;69(2):197-206
AD - Department of Neurology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Cell death in the core of human brain tumors is triggered by hypoxia and lack of nutrients, but the mode of cell death whether necrosis or apoptosis is not clearly defined. To identify the role of apoptosis in brain tumor cell death, we investigated macromolecular (RNA and protein) synthesis and activity in the central to peripheral region of benign [desmoplastic infantile ganglioglioma (DIG) and transitional meningioma (TMG)] and malignant [ependymoma (END), anaplastic astrocytoma (APA), and glioblastoma multiforme (GBM)] brain tumors derived from five patients who had not received previously radiotherapy or chemotherapy. Normal brain tissue (NBT) served as control. RT-PCR analysis of tumor tissues covering central to peripheral regions detected mRNA overexpression of pro-apoptotic gene bax in malignant tumors, indicating a commitment to apoptosis. The mRNA expression of calpain (a Ca(2+)-dependent cysteine protease) and calpastatin (endogenous calpain inhibitor) was altered resulting in an elevated calpain/calpastatin ratio. Calpain content and activity were increased, suggesting a role for calpain in cell death. In the mitochondria-dependent death pathway, caspase-9 and caspase-3 were also overexpressed in tumors. The increased caspase-3 activity cleaved poly(ADP-ribose) polymerase (PARP). Agarose gel electrophoresis detected a mixture of random and internucleosomal DNA fragmentation in malignant brain tumors. Overexpression of pro-apoptotic bax, upregulation of calpain and caspase-3, and occurrence of internucleosomal DNA fragmentation are now presented indicating that one mechanism of cell death in malignant brain tumors is apoptosis, and that enhancement of this process therapeutically may promote decreased tumor growth. Copyright 2002 Wiley-Liss, Inc.
UI - 12134179
AU - Sood S; Sharma NK; Nada M; Dutt A; Nagpal RC
TI - Correlation between CT scan and automated perimetry in supratentorial tumors.
SO - Neurol India 2002 Jun;50(2):158-61
AD - Department of Ophthalmology, Pt. B.D. Sharma Postgraduate Institute of Medical Sciences, Rohtak, 124001, India.
An attempt was made to correlate various types of visual field defects on automated perimetry with the findings of computed tomography in 44 patients of supratentorial tumors. All the patients above the age of 10 years were subjected to complete neurological examination including investigations like plain X-rays and CT scan, however, MRI and angiography were performed wherever indicated. Ocular examination particularly pertaining to neuro-ophthalmological profile was carried out with special emphasis on automated perimetry on Humphrey field analyser. The results indicated that automated perimetry was capable of reliably detecting and quantitating the visual field defects and thus established the location of the tumor in 72% patients when compared to CT scan. Hence, any patient with neuro-ophthalmic features should be subjected to automated perimetry for early diagnosis and probable location of intracranial space occupying lesion affecting visual pathways.
UI - 12037449
AU - Noble JP; Boisnic S; Branchet-Gumila MC; Poisson M
TI - Palmar erythema: cutaneous marker of neoplasms.
SO - Dermatology 2002;204(3):209-13
AD - Consultation de Medecine, Hopital Pitie-Salpetriere, Paris, France.
BACKGROUND: Acral erythema on the palms is observed in several conditions. However, the relationship with malignant tumors has only been reported exceptionally. It should be noted that tumors produce angiogenic mediators. OBJECTIVE: These mediators might promote palmar erythema (PE), and the aim of the present study was to investigate the vasodilation of palmar skin capillaries and angiogenesis, mainly with tumors of the central nervous system. METHODS: In a prospective study of 107 patients affected by brain tumors, we assessed PE clinically and the rate of dilated vessels histologically. We also evaluated the mean surface of the lumen of capillaries on skin biopsies and brain tumors. RESULTS: 6.5% of the patients had an important erythema and 18.5% had slight and/or localized PE. In the skin biopsies, the rate of dilated vessels and the mean surface of the lumen of capillaries were higher than in normal skin. Moreover, the intensity of palmar redness was related to the increase in these vascular changes in the histopathological slices of brain tumors. The intensity also depended on the type of tumor and on its growth. CONCLUSION: The results of the present study strongly suggest that acral erythema is associated with malignant tumors and that the intensity of erythema and the vascular changes of brain tumors are related, probably due to angiogenic factors. Copyright 2002 S. Karger AG, Basel
UI - 11880547
AU - Lopez de Mesa R; Lopez de Cerain Salsamendi A; Ariznabarreta LS;
TI - Abinzano MJ; Patino-Garcia A Measurement and analysis of the chemotherapy-induced genetic instability in pediatric cancer patients.
SO - Mutagenesis 2002 Mar;17(2):171-5
AD - Laboratory and Department of Pediatrics, University of Navarra, E-31080 Pamplona, Spain.
Bleomycin sensitivity has been proven to be a useful biomarker for environmental carcinogenesis and tumor genetic instability. We have previously reported a significant increase in the chromosomal aberrations induced by chemotherapy regimens. This study aimed to test whether there is an inherent increased genetic instability in cancer patients at diagnosis, to determine the increase and time course of the chemotherapy-induced instability and to test whether bleomycin sensitivity can be used as a predictor of tumor evolution or relapse. The analysis included 99 pediatric cancer patients with four different tumor types (Ewing's sarcoma, osteosarcoma, lymphoma and CNS tumors) and 25 controls. Blood samples (n = 171) were obtained before and at the end of treatment, during clinical remission and at relapse and bleomycin tests on lymphocyte cultures were performed. We detected a significant increase (P = 0.004) in mutagen sensitivity in patients at the end of treatment compared with untreated patients, regardless of the tumor type. In both the longitudinal and cross-sectional analyses maximal and similar values of mutagen sensitivity were found in patients during treatment (1.84 +/- 0.82) and at relapse (1.78 +/- 0.52); minimum and simila