Gemistocytic Astrocytoma Research Articles

Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion

Background/Aims: In patients with gliomatosis cerebri (GC), glial fibrillary acidic protein (GFAP) positive cells invade the entire brain, particularly the white matter. Because the nosological definition and histogenesis of GC...

F-18 FDG PET and C-11 MET PET findings in patients with five miscellaneous brain tumors

There are few papers comparing FDG and MET uptake in miscellaneous brain tumors. In the present study, we demonstrated both PET studies of five patients with untreated brain tumors (gemistocytic astrocytoma, tanycytic ependymoma, astroblastoma, gliomatosis cerebri and medulloblastoma). The results show more marked MET uptake into the tumors compared with FDG. As MET PET has an advantage for FDG in delineation of tumor margins, it will be a more promising method to evaluate biological behavior and for instructing surgical procedure or radiotherapy in various brain tumors.

The significance of gemistocytes in astrocytoma.

A retrospective clinical analysis of astrocytomas which contained a significant proportion of gemistocytes was carried out in order to evaluate their effect on prognosis, and other factors influencing prognosis. From 253 consecutive cases of astrocytic tumours in adults, 25 were selected who had more than 20% gemistocytes in every high-power field examined. 9 of these had anaplasia, the remainder did not. They were divided into two groups according to the proportion of gemistocytes; group A, contained more than 60% gemistocytes, and group B, had between 20 and 60% gemistocytes. TUNEL and immunohistochemical staining for PCNA, p53, Ki-67, bcl-2 were performed in the 20 available cases. The median follow-up period was 46 months. There were 14 recurrences, with a median time to recurrence of 15 months. Thirteen repeat operations were performed in nine cases, and two cases showed recurring malignant transformation. The overall median survival time following diagnosis was 73 months and the 5-year survival rate was 52%. There were no significant differences in median survival between groups A and B with different proportions of gemistocytes. On the other hand the median survival of the gemistocytic astrocytomas with anaplasia was 25 months, compared with 158 months for those without anaplasia (p=0.0005). The significant impact of anaplasia on survival persisted in both groups. There were no significant differences in immunohistochemical staining between the two groups, with the exception of staining for Ki-67 (means of the two groups: group A 1.40; group B 2.50). It is suggested that the proportion of gemistocytes does not itself affect prognosis.

PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas.

PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.

Progressive study of recurrent astrocytic tumor

Objective To explore the relationship among the progression, histological types and pathology grade in recurrent astrocytoma. Methods The Clinical and pathological data of 54 cases of recurrent astrocytoma after the second operation were analyzed. Results The pathology grade of 28 cases was progressive and the rate was 51.9%. Anaplastic astrocytoma and gemistocytic astrocytoma showed more progressive and the rate were 66.7%, 78.6%, respectively. Conclusion The result suggested that the age pathology grade and histologyical types were all involved in the astrocytoma progression. Anaplastic astrocytoma and gemistocytic astrocytoma of adults were more progressive.

Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas.

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.

Low-grade hemispheric gliomas in adults: a critical review of extent of resection as a factor influencing outcome.

The goal of this study was to perform a critical review of literature pertinent to low-grade gliomas of the cerebral hemisphere in adults and, on the basis of this review, to evaluate systematically the prognostic effect of extent of resection on survival and to determine if treatment-related guidelines could be established for patients in whom these tumors have been newly diagnosed. Quality of evidence for current treatment options, guidelines, and standards as well as methodological limitations were evaluated. Several prognostic factors thought to affect outcome in patients with low-grade gliomas include the patient's age and neurological status, tumor volume and histological characteristics, and treatment-related variables such as timing of surgical intervention, extent of resection, postoperative tumor volume, and radiation therapy. Patient age and the histological characteristics of the lesion are generally accepted prognostic factors. Among treatment-related factors, timing and extent of resection are controversial because of the lack of randomized controlled trials addressing these issues and the difficulty in obtaining information from available studies that have methodological limitations. All English-language studies on low-grade gliomas published between January 1970 and April 2000 were reviewed. Thirty studies that included statistical analyses were further evaluated with regard to the prognostic effect of extent of resection. Of these 30 studies, those that included pediatric patients, unless adults were analyzed separately, were excluded from further study because of the favorable outcome associated with the pediatric age group. Also excluded were studies including pilocytic and gemistocytic astrocytomas, because the natural histories of these histological subtypes are significantly different from that of low-grade gliomas. Series in which there were small numbers of patients (< 75) were also excluded. Results for oligodendrogliomas are reported separately. Currently, for patients with low-grade glial tumors located in the cerebral hemisphere, the only management standard based on high-quality evidence is tissue diagnosis. All other treatment methods are practice options supported by evidence that is inconclusive or conflicting. The majority of published series that the authors identified had design-related limitations including a small study size, a small number of events (that is, deaths for survival studies), inclusion of pediatric patients, and/or inclusion of various histological types of tumors with different natural histories. Of the 30 series addressing the issue of timing and extent of surgery, almost all had additional design limitations. Methods used to determine the extent of resection were subjective and qualitative in almost all studies. Only five of the 30 series met the authors' criteria, and these studies are discussed in detail. Management of low-grade gliomas is controversial and practice parameters are ill defined. This is caused by limited knowledge regarding the natural history of these tumors and the lack of high-quality evidence supporting various treatment options. Although a prospective randomized study seems unlikely, both retrospective matched studies and prospective observational trials will improve the clinician's ability to understand the importance of various prognostic factors.

Gemistocytic astrocytoma — Astrocytoma II with unfovorable prognosis

Gemistocytic astrocytoma — Astrocytoma II with unfovorable prognosis

Genotype-phenotype correlation in gemistocytic astrocytomas.

Gemistocytic astrocytomas often behave aggressively and carry the least favorable prognosis among diffuse astrocytomas. The frequency of p53 mutations has been reported to be significantly higher in the gemistocytic variant as compared with other astrocytomas. Between 1985 and 1998, we selected 25 tumor samples from among 201 samples from patients with gemistocytic astrocytomas operated on at the Mayo Clinic. Exons 5 to 8 of the p53 gene were sequenced using an automated deoxyribonucleic acid sequencer. Morphometric characterization of individual gemistocytes was performed using an image analysis program. Of 25 tissue samples analyzed, 16 were found to carry a p53 missense mutation (three in exon 5, three in exon 6, one in exon 7, and nine in exon 8), and one sequence variant was synonymous. Mutations were clustered at codons 151 (2 of 17 mutations), 193 (3 of 17 mutations), and 273 (5 of 17 mutations) of the p53 gene. Patients whose tumors carried a p53 mutation were significantly younger than other patients, and their tumors tended to accumulate more p53 protein than those of other patients. Phenotype analysis of gemistocytes revealed that the sizes of tumor cell nuclei and of entire tumor cells in the same tissue area were positively correlated. Smaller tumor cell nuclei tended to be less circular or more atypical. In addition, more atypical gemistocytes were found in tumors lacking a wild-type p53 allele as well as in tissue from patients whose postoperative survival was shorter. Our data confirm that the frequency of p53 mutations is significantly higher (approximately twofold) in gemistocytic astrocytomas as compared with other astrocytoma subtypes. Whether the high frequency of p53 mutations contributes to the more aggressive behavior of gemistocytic astrocytomas, however, remains unclear.

71. The results of postoperative radiotherapy in 63 patients with low-grade gliomas treated in Greatpoland Cancer Center

Low-grade glicomas represents 15% of all primary brain tumors. Between 1990–97 63 patient with low-grade gliomas were treated in Greatpoland Cancer Center (39 males, 24 females; age between 20–60 year). 15 patients had andegrone complete surgical excision, 48 partial or subtotal excision of tumor. The frontal lobe was affected in 33 patients, the temporal lobe in 14 patients. Patients received conventional irradiaton of 60 Gy. *Five patients with histologically verified pilocytic astrocytomas(I) were treated after partial excision, median of age 29.2 year median survival 58 months (27–108). Only one patient died 27 months after radiotherapy. *Thirteen patients with fibrylar astrocytomas(II)-11 post subtotal excision-median age 37.7 year median survival 32.5 months. Recurrent tumor in two patients. Five patients are alive. *Ten patients with protoplasmatic astrocytoma(II)-7 post subtotal excision median of age 43.5 year median survival 30.8 months. Four patients alive. *Seven patients with gemistocytic astrocytomas(II) (6 post subtotal excision)-median age 36 year, median survival 32 months. Only one patient alive. *Eleven patients with oligoastrocytomas(II)-11 post subtotal excision, median age 38.6 year, median survival 43.9 months. Two patients with recrrent tumor. Alive 8 patients. *Seventeen patients with oligodendrogliomas (11 post subtotal excision) median age 39 years, median survival 39 months. One patien with recrrent tumor. Alive 8 patients. *30 patients are alive(48%); *histopathologic diagnosis pilocytic astrocytomas asociated with age 10 years younger then either low-grade gliomas and long-term survivors; *poor prognistic factor in gemistocytic astrocytomas-only one patient alive; *five patients with recurrent tumor among 17 to 49 months after radiotheraphy.

Cytogenetic analysis of gemistocytic cells in gliomas.

Gemistocytes are glial cells characterized by voluminous, eosinophilic cytoplasm and a peripherally positioned, often flattened nucleus. Gemistocytes, usually present in anoxic-ischemic brains, are regularly encountered in glial neoplasms. The presence of gemistocytes in gliomas has been associated with an unfavorable clinical course, notwithstanding the low proliferative potential of these cells. It is not known whether gemistocytes residing in gliomas are dormant tumor cells, or alternatively, represent interspersed reactive glial cells. Whereas gemistocytic astrocytomas have been subject to various genetic investigations, no genomic analysis comparing individual cells in gliomas has been reported so far. In the present study, 3 astrocytomas, 3 oligodendrogliomas, and 3 mixed oligoastrocytomas, all harboring gemistocytic cells, were genetically analyzed by DNA in situ hybridization to paraffin-embedded, formalin-fixed tissue samples with optimal preservation of cellular morphology. To this end, probes for the centromeric regions of chromosome 7 and 10, known to show copy number aberrations in gliomas, were used. In addition, probes for centromeric regions of chromosomes 1 and 17 were used for the ploidy status of the tumors. The spot counts for the various chromosomes were statistically compared. Gains of chromosome 7 were found in 1 anaplastic astrocytoma, 1 anaplastic oligodendroglioma, and 1 anaplastic oligoastrocytoma. Loss of chromosome 10 was seen in 2 anaplastic astrocytomas, in 1 anaplastic oligodendroglioma, and in 1 anaplastic oligoastrocytoma. In 3 cases, significant differences in spot distributions between gemistocytes and non-gemistocytes were found, but the other cases showed no difference in spot distribution. It is concluded that, although many gemistocytic cells in gliomas may be considered reactive cells, in a subset of tumors, part of the gemistocytic cells should be considered neoplastic.

Permanent Iodine-125 Implants in the Treatment of Low-Grade Gliomas

We report a retrospective study on the use of the permanent iodine-125 (125I) implants in the management of low-grade gliomas. From July 1988 to July 1997, 16 patients with low-grade gliomas underwent permanent 125I implants in the management of their lesions. There were 7 males and 9 females ranging in age from 4 to 48 years (mean 19). The location was in the cerebral hemisphere in 7 patients, brainstem in 5 patients and thalamus/basal ganglia in 4 patients. Prior to brachytherapy, 9 patients underwent surgical resection and 7 patients underwent stereotactic biopsy procedures. Fourteen patients were treated as part of the initial management and 2 were recurrent. The histological diagnosis was: 9 WHO grade II astrocytomas, 3 oligodendrogliomas, 2 gemistocytic astrocytomas, 1 pilocytic astrocytoma, and 1 ependymoma. The tumor volume ranged from 0.7 to 33.4 cc (mean 8.4). Stereotactic treatment planning was used to encompass the contrast-enhancing rim of the tumor visualized by computerized tomography with an initial dose rate of 0.05 Gy/hour with 125I. The total activity ranged from 0.8 to 20.5 mCi. With a median follow-up period of 35 months (range, 4–105 months), the 2- and 5-year survival rates were 93.7% and 87.5%, respectively. Three patients underwent reoperation after implants, two of three had recurrent disease, and one had radiation necrosis. Permanent 125I implants appear to be safe and effective as a part of the multimodality management of low-grade gliomas.

Patterns of cyclooxygenase-1 and -2 expression in human gliomas in vivo.

Cyclooxygenases (COX, prostaglandin endoperoxide synthases, PGG/H synthases) are potent mediators of inflammation. While COX-1 is constitutively expressed in a wide range of tissues, COX-2 is cytokine inducible. Although COX-1 expression is observed in normal tissue, enhanced COX-2 expression has been attributed a key role in the development of edema, impeding blood flow and immunomodulation observed in pathologically altered tissues. Here, we have analyzed the expression of COX-1 and COX-2 in 50 gliomas and 10 control brains with no neuropathological alterations by immunohistochemistry; 22 glioblastoma multiforme, 9 anaplastic astrocytomas, 5 protoplasmic astrocytomas, 1 gemistocytic astrocytoma and 13 fibrillary astrocytomas were included in the study. Compared with control brains, accumulation of COX-1 was detected in 20-50% of all cells in both low- and high-grade gliomas. Double-labeling experiments revealed COX-1 expression in subsets of macrophages/microglial cells within the tumor parenchyma and in areas of infiltrative tumor growth. Of the COX-1-positive cells, 90% expressed MHC class II antigens. No COX-1 immunoreactivity was observed in tumor cells. COX-2-positive cells accumulated in tumor cells and in single macrophages/microglial cells in the immediate vicinity of necroses. Further studies are required to determine whether COX-2 is involved in the development of necrosis or, more likely, whether COX-2 is a part of the tumor tissue response to necrosis.

A Correlative Study of Gliomas Using In Vivo Bromodeoxyuridine Labeling Index and Computer-aided Malignancy Grading

An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1–5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme. Copyright 1999 W.B. Saunders Company Ltd on behalf of the Arányi Lajos Foundation

Extracellular matrix-induced cell migration from glioblastoma biopsy specimens in vitro.

The present knowledge about the interaction between the extracellular matrix (ECM) and gliomas is mostly based on studies of permanent cell lines. Since such cultures have undergone an extensive clonal selection in vitro, the experimental results obtained may be quite different from those obtained from studies on true biopsy specimens. The present work demonstrates how different ECM components affect tumor cell migration from human glioblastoma specimens grown as biopsy sample spheroids. Biopsy specimens from 12 glioblastomas and 1 gemistocytic astrocytoma were included in this study. Spheroids were directly initiated from the biopsy specimens, and after 3-4 weeks in culture, they were used in a migration assay. A custom-made filtered medium, where the high molecular weight (>100 kDa) proteins were removed, was supplemented with the following ECM components: laminin, fibronectin, collagen type IV and vitronectin. The cell migration was negligible when spheroids were propagated in the filtered medium. The ECM components as well as complete DMEM evoked strong stimulatory effects on different biopsy specimens. Opposed to that observed earlier for permanent glioma cell lines, highly variable responses were observed between the different biopsy samples on the various ECM components. In general, correlation analyses revealed that specimens that were strongly stimulated by laminin were also stimulated strongly by fibronectin, collagen type IV and vitronectin. This suggests that the capacity to migrate as a response to ECM was confined more to each biopsy specimen than to any specific ECM component. Since biopsy sample spheroids, as original tumors, consist of different cell types, an immunohistochemical characterization of the migrating cells was also performed. Anti-glial fibrillary acidic protein (GFAP) staining revealed both GFAP-positive and -negative migrating cells. Immunostaining for von Willebrand factor and CD11b indicated that the migrating cells were neither endothelial nor microglial cells. This study, therefore, indicates that migratory responses of glioma biopsy specimens to different ECM components is much more heterogeneous than that observed earlier for cell lines. Furthermore, the presented findings support the notion that gliomas may utilize different cell surface receptors for their migration, depending on the cell substrates available.

Simultaneous Alterations of Retinoblastoma and p53 Protein Expression in Astrocytic Tumors

The genetic alterations frequently involved in glial malignancies are in the tumor suppressor genes, Rb and p53. An altered Rb expression or p53 overexpressions is thought to indicate defective tumor supression and subsequently more aggressive tumors. Therefore, to assess the alterations in the conjoint expression of Rb and p53 proteins in formalin fixed paraffin embedded sections, 64 astrolytic tumors were studied (16 astrocytomas, 7 gemistocytic astrocytomas, 19 anaplastic astrocytomas and 22 glioblastomas) using the avidin biotin immunoperoxidase technique. Fifty two cases (81.25%) were found to be positive for p53 protein. Seventeen of these showed aberrant heterogenous staining for pRb, of which 7 were glioblastomas. Only one case of astrocytoma showed aberrant expression of both p53 and Rb. Thus, of the 64 tumors, simultaneous aberrant expression of both p53 and Rb was seen in 21.9% of cases. This was more commonly observed among glioblastoma cases (7/22). No statistical difference was found between the survival rate of heterogenous pRb and p53 positivity in different grades of tumors. In glioblastomas, the survival rate appeared to be less in patients expressing heterogenous pRb, but this was not statistically significant. These results lead us to suspect that p53 and pRb pathways are inactivated, either throught mutation or as part of the neoplastic process in astrocytic tumors.Copyright 1999 W.B. Saunders Company Ltd on behalf of the Arányi Lajos Foundation

Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration

Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. Patients and methods: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19–77). Results: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. Conclusion: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.

Identification in human brain tumors of DNA sequences specific for SV40 large T antigen.

Simian virus 40 (SV40) sequences have recently been identified in a variety of human neoplasms, including mesothelioma, osteosarcoma, and brain tumors, but significant discrepancies exist regarding the frequency at which this occurs. The SV40 genome is 70% homologous to JC and BK, two related polyomaviruses that are highly prevalent in humans and which may cause in immune-compromised patients progressive multifocal leukoencephalopathy (PML) and cystitis, respectively. We have established a specific and sensitive method to identify SV40 sequence in DNA extracted from histological sections, using PCR followed by Southern hybridization to probes specific to the large T region. We found SV40 large T antigen sequences in all brain tumor types investigated. High frequencies were found in low-grade astrocytomas, anaplastic astrocytomas and secondary glioblastomas derived thereof (13/22, 59%) while somewhat lower frequencies were found in gemistocytic astrocytomas (9/28, 32%) and oligodendrogliomas (3/12, 25%). Primary glioblastomas, giant cell glioblastomas, and gliosarcomas, which clinically develop de novo, contained SV40 sequences in 11-25% of cases. Presence of viral DNA was also observed in pediatric brain tumors, including ependymomas (9/16, 56%), choroid plexus papillomas (6/16, 38%), and medulloblastomas (5/17, 29%). In 8 tumor biopsies with SV40 sequences, the adjacent normal brain tissue was also analyzed but was devoid of viral DNA in all but one case. BK and JC virus sequences were rarely detected, the overall frequencies being 3% and 2%, respectively. It remains to be shown whether the presence of SV40 contributes significantly to malignant transformation or whether certain human neoplasms provide a microenvironment that favors viral replication in humans with latent SV40 infection.

Clinical outcome of supratentorial astrocytoma WHO grade II.

There are divergent opinions about the prognostic value of the extent of surgery and of different histological subtypes in supratentorial astrocytomas WHO grade II. We reviewed 75 consecutive patients (36 females, 39 males) with supratentorial astrocytomas WHO grade II (59 primary and 16 recurrent tumours) operated on between 1991 and 1995. Gross total resection could be achieved in 40 astrocytomas, subtotal resection (including biopsy) was performed in 35 cases. Histological assessment confirmed 60 fibrillary, 6 gemistocytic, 9 oligo-astrocytic and no protoplasmic astrocytomas. There were no postoperative deaths. Early outcome 6 to 12 weeks after surgery according to the Glasgow Outcome Scale was good in 46 patients, 24 patients had moderate, and 5 had severe neurological deficits. Survival rates 1, 2, 3, and 4 years following surgery were 100%, 96%, 96%, 96% for patients who underwent gross total tumour resection and 86%, 77%, 77%, 64% for patients with subtotal tumour resection. The cumulative recurrence or progression rates after 4 years were 26% after gross total resection and 80% after subtotal resection, and this result is statistically significant. Recurrences after gross total resection or progressions after subtotal resection occurred more often in gemistocytic astrocytomas (40% and 100%, respectively) than in other subtypes. Dedifferentiation to a more malignant tumour seems to be more prominent in the gemistocytic subtype. Gross total resection should be the leading therapeutic option for patients with astrocytomas WHO grade II. For the gemistocytic subtype further studies will have to prove whether additional radiotherapy is of any benefit.

P53 and PTEN gene mutations in gemistocytic astrocytomas.

The gemistocytic astrocytoma is a histological variant of diffuse astrocytomas and is characterised by the presence of large, GFAP-expressing neoplastic astrocytes (gemistocytes) and a tendency towards rapid progression to glioblastoma. In this study, we analyzed 28 gemistocytic astrocytomas (mean fraction of gemistocytes, 35.0+/-9.9%) for mutations in the p53 and PTEN (MMAC1) tumour suppressor genes. Single strand conformation polymorphism (SSCP), followed by direct DNA sequencing of p53 exons 5-8, revealed a mutation in 23 of 28 (82%) cases. Regional analysis of four tumours revealed identical p53 mutations in gemistocytic and fibrillary tumour areas. In contrast, none of 15 gemistocytic astrocytomas (WHO Grade II) and only two of 11 (18%) anaplastic gemistocytic astrocytomas (WHO Grade III) contained a PTEN mutation. Of these, one was a 1 bp deletion in codon 345 and the other a 1 bp insertion in intron 4. Differential PCR did not reveal homozygous PTEN deletion in any of the tumours analysed. These results indicate that p53 mutations are a genetic hallmark of gemistocytic astrocytomas, whilst PTEN mutations are absent in low-grade and rare in anaplastic gemistocytic astrocytomas.