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Paul Kleihues

Publications and source records attributed to Paul Kleihues.

At least 19 recordsLinked to original sources
PubMed2006

Stratification of medulloblastoma on the basis of histopathological grading.

Medulloblastoma (WHO grade IV) is an embryonal tumour of the cerebellum and the most common malignant central nervous system tumour in children. Despite significant advances in treatment, 5-year survival rates are still less than 70%, suggesting the presence of subgroups with different response to radio/chemotherapy. In the present study, we re-evaluated a series of 347 medulloblastomas from the SIOP II clinical trial of the International Society of Paediatric Oncology to identify features predictive of clinical outcome. Relapse free survival for medulloblastomas with severe anaplasia [5-year rate: S(60)=49.5%], was significantly shorter than for tumours with moderate or mild anaplasia S(60)=65.4%; P=0.001). The difference between both groups was even larger when the presence or absence of extensive apoptosis was included (46.5 vs. 66.7%; P=0.0216). Other histological features including nodularity, necrosis, vascular proliferation and the presence of beta-catenin mutations (7% of cases) were not predictive for relapse free survival. These findings indicate that degree of anaplasia is the most significant histologic feature predictive of the survival of medulloblastoma patients.

Adolescent↗
PubMed2006

Brain tumors in S100beta-v-erbB transgenic rats.

We have established a line of transgenic rats expressing v-erbB, the viral form of epidermal growth factor receptor (EGFR), under transcriptional regulation of the S100beta promoter. Reverse transcriptase-polymerase chain reaction revealed highest transgene expression in the cerebellum followed by the cerebrum, ovary, and testis. Other organs, including the lung, heart, salivary gland, colon, liver, kidney, and spleen, did not show detectable transgene expression. Of 23 homozygous rats that died or were killed because they became moribund between 25 and 91 weeks of age, 15 (65%) showed the presence of brain tumors (mean age, 59 weeks). Of the 10 heterozygous rats killed between 61 and 91 weeks of age, 4 (40%) showed the presence of brain tumors (mean, 77 weeks). With 3 exceptions, all tumors were located within or near the cerebellum (83%). There were 2 major histologic types; one type displayed a solid growth pattern with predominantly perivascular infiltration of adjacent central nervous system tissue and the meninges. Tumors showed histologic features of malignancy with occasional lung metastases. There was a consistent, strong immunoreactivity for S100 protein but no significant expression of glial, neuronal, or meningothelial markers. These tumors were classified as malignant gliomas. A second tumor type was less invasive and characterized by isomorphic cells with round to ovoid nuclei and clear perinuclear halos expressing S100 but no neuronal or glial marker proteins. They were diagnosed as oligodendrogliomas. This is the first transgenic rat model that spontaneously develops brain tumors. Because v-erbB is structurally and functionally similar to the truncated form of EGFR amplified and overexpressed in human glioblastomas, S100beta-v-erbB transgenic rats may serve as a useful animal model for the identification of EGFR-related molecular targets and as a tool for the assessment of novel therapeutic approaches.

Animals↗
PubMed2005

Epidemiology and etiology of gliomas.

Gliomas of astrocytic, oligodendroglial and ependymal origin account for more than 70% of all brain tumors. The most frequent (65%) and most malignant histological type is the glioblastoma. Since the introduction of computerized tomography and magnetic resonance imaging, the incidence rates of brain tumors have been rather stable, with a tendency of higher rates in highly developed, industrialized countries. Some reports indicate that Caucasians have higher incidence than black or Asian populations, but to some extent, this may reflect socio-economic differences and under-ascertainment in some regions, rather than a significant difference in genetic susceptibility. With the exception of pilocytic astrocytomas, the prognosis of glioma patients is still poor. Less than 3% of glioblastoma patients are still alive at 5 years after diagnosis, higher age being the most significant predictor of poor outcome. Brain tumors are a component of several inherited tumor syndromes, but the prevalence of these syndromes is very low. Several occupations, environmental carcinogens, and diet (N-nitroso compounds) have been reported to be associated with an elevated glioma risk, but the only environmental factor unequivocally associated with an increased risk of brain tumors, including gliomas, is therapeutic X-irradiation. In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumor (PNET), often within 10 years after therapy. TP53 mutations are frequent in low-grade gliomas and secondary glioblastomas derived therefrom. Approximately 60% of mutations are located in the hot spot codons 248 and 273, and the majority of these are G:C-->A:T transitions at CpG sites. TP53 mutations are significantly more frequent in low-grade astrocytomas with promoter methylation of the O(6)-methylguanine-DNA methyltransferase repair gene, suggesting that, in addition to deamination of 5-methylcytosine, exogenous or endogenous alkylation in the O(6) position of guanine may contribute to the formation of these mutations.

Age Factors↗
PubMed2005

Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas.

Published data on prognostic and predictive factors in patients with gliomas are largely based on clinical trials and hospital-based studies. This review summarizes data on incidence rates, survival, and genetic alterations from population-based studies of astrocytic and oligodendrogliomas that were carried out in the Canton of Zurich, Switzerland (approximately 1.16 million inhabitants). A total of 987 cases were diagnosed between 1980 and 1994 and patients were followed up at least until 1999. While survival rates for pilocytic astrocytomas were excellent (96% at 10 years), the prognosis of diffusely infiltrating gliomas was poorer, with median survival times (MST) of 5.6 years for low-grade astrocytoma WHO grade II, 1.6 years for anaplastic astrocytoma grade III, and 0.4 years for glioblastoma. For oligodendrogliomas the MSTwas 11.6 years for grade II and 3.5 years for grade III. TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but infrequent (13%) in oligodendrogliomas. LOH 1p/19q typically occurred in tumors without TP53 mutations and were most frequent in oligodendrogliomas (69%), followed by oligoastrocytomas (45%), but were rare in fibrillary astrocytomas (7%) and absent in gemistocytic astrocytomas. Glioblastomas were most frequent (3.55 cases per 100,000 persons per year) adjusted to the European Standard Population, amounting to 69% of total incident cases. Observed survival rates were 42.4% at 6 months, 17.7% at one year, and 3.3% at 2 years. For all age groups, survival was inversely correlated with age, ranging from an MST of 8.8 months (<50 years) to 1.6 months (>80 years). In glioblastomas, LOH 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations, and was the only alteration associated with shorter survival of glioblastoma patients. Primary (de novo) glioblastomas prevailed (95%), while secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hot-spot codons 248 and 273, while in primary glioblastomas, mutations were more evenly distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas, suggesting that the acquisition of TP53 mutations in these glioblastoma subtypes may occur through different mechanisms.

Age Distribution↗
PubMed2004

Genetic pathways to glioblastoma: a population-based study.

We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (<50 years) to 1.6 months (>80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

Adult↗
PubMed2004

Gene expression profiling and subgroup identification of oligodendrogliomas.

The histological diagnosis of low-grade astrocytomas and oligodendrogliomas (WHO grade II) is often challenging, particularly in cases that show both astrocytic and oligodendroglial differentiation. We carried out gene expression profiling on 17 oligodendrogliomas (93% with LOH 1p and/or 19q) and 15 low-grade astrocytomas (71% with a TP53 mutation), using a cDNA array containing 1176 cancer-related genes. In oligodendrogliomas, 40 genes showed on average higher expression (at least a two-fold increase) than in astrocytomas, including DES, TDGF1, TGF-beta, GABA-BR1A, Histone H4, CDKN1A, PCDH43, Rho7 and Jun-D, while 39 genes were expressed at lower levels (at least a two-fold decrease), including JNK2, ITGB4, JNK3A2, RhoC, IFI-56K, AAD14 and EGFR. Immunohistochemistry revealed nuclear staining of Jun-D in oligodendrogliomas, in contrast to the immunoreactivity of cytoplasm and cell processes in low-grade astrocytomas. Partial least-squares analysis of the 79 genes at least two-fold differentially expressed between oligodendrogliomas and low-grade astrocytomas demonstrated perfect separation of oligodendrogliomas from low-grade astrocytomas and normal cerebral white matter. Clustering analysis based on the entire gene set divided the 17 subjects with oligodendrogliomas into two subgroups with significantly different survival (log-rank test, P=0.0305; survival to 5-years, 80 vs 0%, P=0.048). These results demonstrate that oligodendrogliomas and low-grade astrocytomas differ in their gene expression profiles, and that there are subgroups of oligodendroglioma with distinct expression profiles related to clinical outcome.

Adult↗
PubMed2004

Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas.

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5+/-4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (<50 years) survived significantly longer than older patients (>50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma ( P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (1p, 27%; 19q, 45%), rare in fibrillary astrocytomas (1p, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multivariate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

Age Factors↗
PubMed2004

Molecular pathogenesis of astrocytic tumours.

Our current knowledge of the molecular pathogenesis of the diffuse adult astrocytic tumours is vast if compared to 20 years ago, yet we are far from understanding the details of this process at the molecular level and using such an understanding to logically and specifically treat patients' tumours. In other astrocytic tumours we have little or no knowledge of the molecular processes. This article will attempt to summarise the histological classification criteria and genetic data for all the astrocytic tumours. The current World Health Organisation classification lists six entities, some with subgroups. Common problems associated with the diagnosis of these tumours are outlined. While the molecular findings are not as yet used clinically, we are approaching a time when the histological investigation will have to be supplemented with molecular data to ensure the best choice of treatment for the patient and as an accurate indicator of prognosis.

Adult↗
PubMed2004

Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas.

EGFR amplification is a frequent genetic alteration in primary (de novo) glioblastomas, and is often associated with structural alterations. Most common is variant III (EGFRvIII), which results from a non-random 801 bp in-frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and overexpression of EGFRvIII and wild-type EGFR in 30 glioblastoma biopsies. Immunohistochemically, EGFR overexpression was observed in 20 (67%) of 30 glioblastomas. Eight (27%) cases also showed immunoreactivity to an EGFRvIII antibody. In 6 of these cases, the pattern of EGFR and EGFRvIII overexpression was compared in serial sections: In 4 cases, areas with immunoreactivity to EGFRvIII largely coincided with wild-type EGFR expression. In the other 2 cases, the areas immunoreactive to EGFRvIII were significantly less extensive than EGFR-positive areas. To assess whether EGFRvIII is predominantly amplified in tumors with concurrent wild-type EGFR amplification, we carried our real-time quantitative PCR using 2 sets of primers located in exon 2 and intron 15 of the EGFR gene. A > 5-fold ratio of relative copy numbers between intron 15 (present both in wild-type EGFR and EGFRvIII) and exon 2 (present only in wild-type EGFR, but missing in EGFRvIII) suggested predominant amplification of EGFRvIII in only 3 (10%) of 30 glioblastomas. The observation that intratumoral wild-type EGFR overexpression is often more extensive and that predominant amplification of EGFRvIII is a rare event would limit the effectiveness of therapeutic approaches based on selective targeting of EGFRvIII.

Adult↗
PubMed2004

Genetic and expression profiles of cerebellar liponeurocytomas.

Cerebellar liponeurocytoma, a rare, newly identified CNS neoplasm of adults, is characterized by advanced neuronal/neurocytic and focal lipomatous differentiation, low proliferative potential and a favorable clinical prognosis. Despite the different age distribution and benign biological behavior, the cerebellar liponeurocytoma shares several features with the cerebellar medulloblastoma, which may include an origin from the periventricular matrix of the fourth ventricle or the external granular layer of the cerebellum. To establish the genetic profile of cerebellar liponeurocytomas, we have formed an international consortium and collected tumor samples from 20 patients. DNA sequencing revealed TP53 missense mutations in 4 (20%) of 20 cerebellar liponeurocytomas, a frequency higher than in medulloblastomas. There was no case with PTCH, APC, or beta-catenin mutations, each of which may be present in subsets of medulloblastomas. Isochromosome 17q, a genetic hallmark of classic medulloblastomas, was not observed in any of the cases investigated by FISH analysis. cDNA array analyses were carried out on 4 cerebellar liponeurocytomas, 4 central neurocytomas, and 4 classic medulloblastomas. Cluster analysis of the cDNA expression data of 1176 genes grouped cerebellar liponeurocytomas close to central neurocytomas, but distinct from medulloblastomas. These results suggest cerebellar liponeurocytoma as a distinct tumor entity that is genetically different from medulloblastoma. Furthermore, the cDNA expression array data suggest a relationship to central neurocytomas, but the presence of TP53 mutations, which are absent in central neurocytomas, suggests that their genetic pathways are different.

Adult↗
PubMed2004

The science and practice of carcinogen identification and evaluation.

Several national and international health agencies have established programs with the aim of identifying agents and exposures that cause cancer in humans. Carcinogen identification is an activity grounded in the scientific evaluation of the results of human epidemiologic studies, long-term bioassays in experimental animals, and other data relevant to an evaluation of carcinogenicity and its mechanisms. In this commentary, after a brief discussion of the science basis common to the evaluation of carcinogens across different programs, we discuss in more detail the principles and procedures currently used by the IARC Monographs program.

Biological Assay↗
PubMed2003

Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.

A database has been created to collect information on families carrying a germ-line mutation in the TP53 gene and on families affected with Li-Fraumeni syndromes [Li-Fraumeni syndrome (LFS) and Li-Fraumeni-like syndrome (LFL)]. Data from the published literature have been included. The database is available online at http://www.iarc.fr/p53, as part of the IARC TP53 Database. The analysis of the 265 families/individuals that have been included thus far has revealed several new findings. In classical LFS families with a germ-line TP53 mutation (83 families), the mean age of onset of breast cancer was significantly lower than in LFS families (16 families) without a TP53 mutation (34.6 versus 42.5 years; P = 0.0035). In individuals with a TP53 mutation, a correlation between the genotype and phenotype was found. Brain tumors were associated with missense TP53 mutations located in the DNA-binding loop that contact the minor groove of DNA (P = 0.01), whereas adrenal gland carcinomas were associated with missense mutations located in the loops opposing the protein-DNA contact surface (P = 0.003). Finally, mutations likely to result in a null phenotype (absence of the protein or loss of function) were associated with earlier onset brain tumors (P = 0.004). These observations have clinical implications for genetic testing and tumor surveillance in LFS/LFL families.

Adolescent↗
PubMed2003

PTEN methylation and expression in glioblastomas.

The tumor suppressor gene PTEN on chromosome 10q23.3 regulates the Akt signaling pathway and modulates cell growth and apoptosis. The PTEN gene is mutated in 20-40% of glioblastomas. In this study, we assessed whether loss of PTEN expression is also caused epigenetically. Methylation-specific PCR revealed that CpG islands of the PTEN promoter were methylated in 27 of 77 (35%) glioblastomas and in 4 of 11 (36%) glioblastoma cell lines. Only two glioblastomas showed loss of PTEN immunoreactivity in the entire biopsy; both had a missense PTEN mutation and LOH at the PTEN locus, but lacked PTEN methylation. In biopsy specimens with focal loss of PTEN expression, DNA samples extracted from microdissected foci showed PTEN methylation only in areas with loss of PTEN expression. These results suggest that PTEN methylation occurs frequently in glioblastomas and may be associated with focal loss of PTEN expression. However, the correlation between PTEN methylation, PTEN mutations, LOH at the PTEN locus, and loss of PTEN protein expression was inconsistent. Possible reasons for discrepancies between gene status and protein expression include differences in the biological effect of specific PTEN mutations and the possibility that the processed PTEN pseudogene on 9p21 is expressed in glioblastomas and co-reacts with the PTEN antibody.

Adult↗
PubMed2003

AXIN1 mutations but not deletions in cerebellar medulloblastomas.

Medulloblastoma is a malignant, invasive embryonal tumour of the cerebellum which manifests preferentially in children. A subset of cases is associated with colon cancer and APC germline mutations (Turcot syndrome), and APC and beta-catenin point mutations occur in up to 10% of sporadic cases, indicating the involvement of the Wnt pathway in the development of medulloblastoma. In 39 sporadic cerebellar medulloblastomas screeened for alterations in the AXIN1 gene, another component of the Wnt pathway, we found missense AXIN1 mutations in two tumours, CCC-->TCC at codon 255 (exon 1, Pro-->Ser) and TCT-->TGT at codon 263 (exon 1, Ser-->Cys). Furthermore, the A allele at the G/A polymorphism at nucleotide 16 in intron 4 was significantly over-represented in medulloblastomas (39 cases; G 0.76 vs-A 0.24) compared to healthy individuals (86 cases; G 0.91 vs A 0.09; P=0.0027). RT-PCR revealed large deletions in the AXIN1 gene in 5/12 (42%) medulloblastomas, consistent with a previous report. However, we observed such deletions at a similar frequency also in normal brain tissue (6/12, 50%). Since there are multiple complementary, inverted sequences present in the AXIN1 gene, these large deletions may represent RT-PCR errors due to stem-loop secondary structures.

Axin Protein↗
PubMed2003

Null mutation of DNA strand break-binding molecule poly(ADP-ribose) polymerase causes medulloblastomas in p53(-/-) mice.

Medulloblastoma is an invasive embryonal tumor of the cerebellum with predominant neuronal differentiation. Although several genes have been implicated in medulloblasoma formation, such as Patched (Ptc1) and the adenomatous polyposis coli gene (Apc), the majority of these tumors cannot be explained by mutations in these genes. The cellular origin as well as the genetic and molecular changes involved in the genesis and progression of human medulloblastomas remain largely unknown. Here we show that disruption of poly(ADP-ribose) polymerase (PARP-1) causes a high incidence (49%) of aggressive brain tumors in p53 null mice, with typical features of human cerebellar medulloblastomas. At as early as 8 weeks of age, lesions started on the outer surface of the cerebellum from remnant granule cell precursors of the developmental external germinal layer. Progression of these tumors is associated with the re-activation of the neuronal specific transcription factor Math1, dysregulation of Shh/Ptc1 signaling pathway, and chromosomal aberrations, including triradial and quadriradial chromosomes. The present study indicates that the loss of function of DNA double-strand break-sensing and repair molecules is an etiological factor in the evolution of the cerebellar medulloblastomas. These PARP-1/p53 double null mice represent a novel model for the pathogenesis of human medulloblastomas.

Animals↗
PubMed2003

Cerebellar liponeurocytoma with an unusually aggressive clinical course: case report.

OBJECTIVE AND IMPORTANCE: Liponeurocytomas are rare cerebellar neoplasms in adults, with benign histological features and a favorable clinical prognosis. Current clinical opinion is based on a total of less than 20 published cases and suggests that gross total resection and long-term follow-up monitoring, with possible additional surgery and radiotherapy for treatment of recurrent tumors, represent the best treatment approach for this relatively benign tumor type. CLINICAL PRESENTATION: A 51-year-old Caucasian woman presented with worsening unsteady gait and headaches, suggesting increased intracranial pressure. INTERVENTION: The patient underwent subtotal resection of a cerebellar liponeurocytoma, followed by fractionated radiotherapy (total dose of 54 Gy). She experienced a local recurrence of the tumor 12 months later and underwent additional surgery for removal of the cerebellar mass. A second recurrent tumor was diagnosed on magnetic resonance imaging scans 3 months later and was surgically resected. The tumor histological findings were consistently devoid of atypical features, apart from leptomeningeal invasion noted in the first surgical specimen. CONCLUSION: This unusual case demonstrated an atypical clinical course of a highly aggressive and radiation-resistant tumor, despite the consistent absence of aggressive histological features. Cerebellar liponeurocytomas may not be as benign as the current literature and typical low-grade cytological and histological features suggest.

Cerebellar Neoplasms↗
PubMed2003

A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma.

OBJECT: The incidence of pilocytic astrocytomas and the rate of patient survival were analyzed in a population-based study in the canton of Zürich, Switzerland. METHODS: Between 1980 and 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 55 (5.5%) were pilocytic astrocytomas. The incidence rate, adjusted to the World Standard Population, was 4.8 per 1 million per year. The mean age at clinical diagnosis was 19.6 +/- 12.7 years, and the male/female ratio was 1.12. The most frequent tumor sites were the cerebellum (40%), followed by supratentorial locations (35%), the optic pathway and hypothalamus (11%), and the brainstem (9%). The mean follow-up period was 12 years. Observed survival rates were 100% at 5 years and 95.8% at 10 years after diagnosis (relative survival rate at 10 years: 96.8%). Seven patients (13%) received postoperative radiotherapy, but this did not significantly affect survival. In all patients the tumors were histologically classified as WHO Grade I, except in two patients who had anaplastic pilocytic astrocytoma (Grade III), one of whom died after 7 years, whereas the other was still alive after 10 years. CONCLUSIONS: This population-based study shows that, because of the benign biological behavior of pilocytic astrocytomas and advances in microneurosurgery, the survival rates for patients with these tumors are excellent, regardless of postoperative radiotherapy.

Adult↗