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Technology in Cancer Research &... Jun 2006Gliomas, the most frequent primary brain tumors in humans, form a heterogeneous group, encompassing many different histological types and malignancy grades. Within this... (Review)
Review
Gliomas, the most frequent primary brain tumors in humans, form a heterogeneous group, encompassing many different histological types and malignancy grades. Within this group, the diffuse infiltrative gliomas are by far the most common in adults. The major representatives in this subgroup are the diffuse astrocytic, oligodendroglial, and mixed oligo-astrocytic tumors. Especially in these diffuse gliomas, the role of molecular diagnostics is rapidly increasing. After summarizing the most relevant genetic aberrations and pathways in these tumors detected up till now, this review will discuss the clinical relevance of this information. Several molecular markers have been identified in diffuse gliomas that carry diagnostic and prognostic information. In addition, some of these and other markers predict the response of these gliomas to particular (chemo)therapeutic approaches. The techniques used to obtain this molecular information, as well as the advantages and disadvantages of the different techniques will be discussed. Finally, future perspectives will be presented with regard to the contribution of molecular diagnostics to tailor-made therapy in glioma patients.
Topics: Biomarkers, Tumor; Brain Neoplasms; Cell Cycle Proteins; DNA Methylation; DNA Repair; Gene Dosage; Glioma; Humans; Molecular Diagnostic Techniques; Neovascularization, Pathologic; Receptor Protein-Tyrosine Kinases; Retinoblastoma Protein; Tumor Suppressor Protein p53
PubMed: 16700618
DOI: 10.1177/153303460600500305 -
Folia Neuropathologica 2012Since the recent publication of the World Health Organization brain tumour classification guidelines in 2007, a significant expansion in the molecular understanding of... (Review)
Review
Since the recent publication of the World Health Organization brain tumour classification guidelines in 2007, a significant expansion in the molecular understanding of glioblastoma multiforme (GBM) and its pathological as well as genomic variants has been evident. The purpose of this review article is to evaluate the histopathological, molecular and clinical features surrounding emerging and currently established GBM variants. The tumours discussed include classic glioblastoma multiforme and its four genomic variants, proneural, neural, mesenchymal, classical, as well as gliosarcoma (GS), and giant cell GBM (gcGBM). Furthermore, the emerging variants include fibrillary/epithelial GBM, small cell astrocytoma (SCA), GBM with oligodendroglial component (GBMO), GBM with primitive neuroectodermal features (GBM-PNET), gemistocytic astrocytoma (GA), granular cell astrocytoma (GCA), and paediatric high-grade glioma (HGG) as well as diffuse intrinsic pontine glioma (DIPG). Better understanding of the heterogeneous nature of GBM may provide improved treatment paradigms, prognostic classification, and approaches towards molecularly targeted treatments.
Topics: Brain Neoplasms; Glioblastoma; Humans
PubMed: 23319187
DOI: 10.5114/fn.2012.32361 -
Turkish Neurosurgery 2022To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children.
AIM
To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children.
MATERIAL AND METHODS
Files (2006 to 2020) of children diagnosed with glial tumors and followed-up were reviewed retrospectively. Information regarding demographic and clinical characteristics, treatment approaches, and outcomes were retrieved from the patients? files.
RESULTS
Of the total of 180 pediatric patients diagnosed with brain tumors, 73 (40.6%) had glial tumors. The children with astrocytoma were in the age range of 2?18 years (median age: 8.7 years), while the ages of children with ependymoma ranged from three months to 10 years (median age: 3 years). This difference was statistically significant (p < 0.0001). The male to female ratio was 1.6. The most common symptoms or signs were headaches (n=34, 46.6%), abnormal gait or coordination (n=22, 30.2%), vomiting (n=21, 28.8%), and cranial nerve palsies (n=20, 27.4%). The pathological diagnoses were astrocytomas (n=53, 72.6%), oligodendroglial tumors (n=2, 2.7%), ependymoma (n=15, 20.7%), and other glial tumors (n=3, 4.1%). The most common tumor location was supratentorial (n=42, 57.5%), while midline glioma was detected in seven patients. The 5-year overall survival (OS) rate of all glial tumors, astrocytoma, and ependymoma was 42%, 40%, and 55%, respectively. The 5-year OS rate of the tumor Grade I, II, III, and IV was 77.2%, 45%, 32%, and 0%, respectively (p < 0.0001). The 5-year OS rate of supratentorial, infratentorial, and spinal tumors was 25.6%, 63.6%, and 50%, respectively (p=0.021). In Cox regression analysis, it was found that the tumor resection and grade had an effect on the tumor prognosis.
CONCLUSION
Treatment results are not satisfactory in high-grade astrocytomas. There is a need for new treatment approaches that would take cognizance of molecular features and adopt multidisciplinary approaches.
Topics: Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Female; Glioma; Humans; Infant; Male; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 34751424
DOI: 10.5137/1019-5149.JTN.34801-21.2 -
The American Journal of Pathology Mar 1994The origin and nature of central nervous system tumors primarily composed of primitive neuroepithelial cells have intrigued neuropathologists since 1925, when the... (Review)
Review
The origin and nature of central nervous system tumors primarily composed of primitive neuroepithelial cells have intrigued neuropathologists since 1925, when the prototype tumor in this group, the medulloblastoma, was defined as a specific type by Bailey and Cushing. Theories regarding this group of tumors have been widely divergent, ranging from classification as sarcomas, neuroblastomas, spongioblastomas, ie, poorly differentiated gliomas (including astrocytic, oligodendroglial, and ependymal), to primitive tumors with a capacity for multidirectional differentiation. Studies of both human and experimental primitive neuroectodermal tumors have yielded considerable information about biological features, although controversies remain regarding interpretation of the findings. Moreover, many investigators remain fixed upon the notion that discovery of the "cell of origin" of these tumors will somehow enhance understanding of their nature. Rationale for relevance of this view is examined against the current state of knowledge regarding carcinogenesis as a whole and studies of human and experimental primitive neuroectodermal tumors in particular, and it is concluded that the time has come to discard the archaic concept of cell of origin and devote resources to investigations of the phenotypic character of the tumor and its relationship to prognosis and treatment.
Topics: Animals; Brain Neoplasms; Humans; Neoplasms, Experimental; Neuroectodermal Tumors, Primitive; Phenotype
PubMed: 8129029
DOI: No ID Found -
Virchows Archiv : An International... Nov 2021Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated... (Comparative Study)
Comparative Study
Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. The latter is mutually exclusive to ATRX immunohistochemical loss and has been recently associated with the loss of H3K27me3 immunostaining. We aimed to assess the diagnostic and prognostic value of H3K27me3 immuno-expression in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. H3K27me3 immunostaining was performed in 69 diffuse gliomas with oligodendroglial (n = 62) or oligoastrocytic (n = 7) morphology. The integration with routinely assessed IDH mutations, ATRX immunostaining, and 1p/19q codeletion classified these cases as 60 oligodendroglial and 9 astrocytic. H3K27me3 was lost in 58/60 oligodendrogliomas with retained (n = 47) or non-conclusive (n = 11) ATRX staining, 3/6 IDH-mutant astrocytomas with ATRX loss, and 3/3 IDH-wt astrocytomas. H3K27me3 was retained in 2/60 oligodendrogliomas with retained ATRX, and in 3/6 IDH-mutant astrocytomas, two of which had lost and one retained ATRX. The combination of H3K27me3 and ATRX immunostainings with IDH mutational status correctly classified 55/69 (80%) cases. In IDH-mutant gliomas, ATRX loss indicates astrocytic phenotype, while ATRX retention and H3K27me3 loss identify oligodendroglial phenotype. Only 14 (20%) IDH-mutant cases with retained ATRX and H3K27me3 or inconclusive ATRX immunostaining would have requested 1p/19q codeletion testing to be classified. Furthermore, H3K27me3 retention was associated with significantly shorter relapse-free survival (P < 0.0001), independently from IDH mutation or 1p/19q codeletion (P < 0.005). Our data suggest that adding H3K27me3 immunostaining to the diagnostic workflow of diffuse gliomas with oligodendroglial or mixed morphology is useful for drastically reducing the number of cases requiring 1p/19q codeletion testing and providing relevant prognostic information.
Topics: Adult; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Female; Histones; Humans; Immunohistochemistry; Isocitrate Dehydrogenase; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local; Oligodendroglioma; Predictive Value of Tests; Progression-Free Survival; Time Factors; X-linked Nuclear Protein
PubMed: 34165590
DOI: 10.1007/s00428-021-03134-1 -
Neuro-oncology Jan 1999Over the past three decades, we have made great strides in the treatment of most, but not all, brain tumors. Dramatic advances have occurred in diagnostic imaging,... (Review)
Review
Over the past three decades, we have made great strides in the treatment of most, but not all, brain tumors. Dramatic advances have occurred in diagnostic imaging, neurosurgery, neuroanesthesia, radiotherapy, and chemotherapy for CNS tumors. Unfortunately, our progress has not yet met our expectations. Because of the infiltrative nature of most primary brain tumors, neurosurgery can never be expected to be curative for the majority of gliomas. Because infiltrative tumors interdigitate with normal brain cells and are not highly sensitive to irradiation, one cannot expect radiotherapy to be curative without serious damage to normal brain cells. The hope for a cure, then, rests with chemotherapy. Those who administer chemotherapy to patients with CNS tumors fully expect that, in time, long-term survival and, ultimately, the cure will become an everyday reality. To achieve that reality, however, new treatment concepts and drugs are needed.
Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Astrocytoma; Brain Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Forecasting; Glioblastoma; Humans; Immunologic Factors; Injections, Intra-Arterial; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Oligodendroglioma; Palliative Care; Signal Transduction; Survival Analysis
PubMed: 11550304
DOI: 10.1093/neuonc/1.1.69 -
Journal of Clinical Oncology : Official... Aug 2022JCO Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization...
JCO Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization for the Research and Treatment of Cancer 26951 and Radiation Therapy Oncology Group 9402 phase III trials initiated in 1990s, which both studied radiotherapy with/without neo/adjuvant procarbazine, lomustine, and vincristine (PCV) for newly diagnosed anaplastic oligodendroglial tumors. The median follow-up duration in both was 18-19 years. For European Organization for the Research and Treatment of Cancer 26951, median, 14-year, and probable 20-year overall survival rates without versus with PCV were 2.6 years, 13.4%, and 10.1% versus 3.5 years, 25.1%, and 16.8% (N = 368 overall; hazard ratio [HR] 0.78; 95% CI, 0.63 to 0.98; = .033), with 1p19q codeletion 9.3 years, 26.2%, and 13.6% versus 14.2 years, 51.0%, and 37.1% (n = 80; HR 0.60; 95% CI, 0.35 to 1.03; = .063), respectively. For Radiation Therapy Oncology Group 9402, analogous results were 4.8 years, 16.5%, and 11.2% versus 4.8 years, 29.1%, and 24.6% (N = 289 overall; HR 0.79; 95% CI, 0.61 to 1.03; = .08), with codeletion 7.3 years, 25.0%, and 14.9% versus 13.2 years, 46.1%, and 37% (n = 125; HR 0.61; 95% CI, 0.40 to 0.94; = .02), respectively. With that, the studies show similar long-term survival even without tumor recurrence in a significant proportion of patients after first-line treatment with radiotherapy/PCV.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Clinical Trials, Phase III as Topic; Humans; Lomustine; Neoplasm Recurrence, Local; Oligodendroglioma; Procarbazine; Vincristine
PubMed: 35731991
DOI: 10.1200/JCO.21.02543 -
Neurology India 2018The plethora of biomarkers available for the diagnosis and prognostication of gliomas has refined the classification of gliomas. The new World Health Organization (WHO)...
BACKGROUND
The plethora of biomarkers available for the diagnosis and prognostication of gliomas has refined the classification of gliomas. The new World Health Organization (WHO) 2016 classification integrates the phenotypic and genotyping features for a more robust diagnosis.
MATERIALS AND METHODS
Fifty gliomas with oligodendroglial morphology according to the WHO 2007 classification were analyzed for isocitrate dehydrogenase 1 and 2 (IDH1/2) mutations by polymerase chain reaction, 1p/19q status by fluorescent in situ hybridization (FISH), and IDH1 and X-linked alpha-thalassemia retardation (ATRX) expression by immunohistochemistry. Tumors were reclassified into oligodendrogliomas, astrocytomas, and glioblastomas (GBMs) according to the new "integrated" diagnostic approach.
RESULTS
30% of previously diagnosed oligodendrogliomas and almost 90% of oligoastrocytomas were reclassified as astrocytomas. Twenty gliomas showed 1p/19q co-deletion, while 18 gliomas showed polysomy of chromosome 1/19. Polysomy of chromosome 1/19 was significantly associated with astrocytic tumors (P ≤ 0.001). Loss of ATRX expression was seen in 20 of 23 WHO grade II/III astrocytomas and 3 of 7 GBMs. All WHO grade II and III gliomas in our cohort showed IDH1/2 mutations. Moreover, 4 of 7 GBMs showed the wild-type IDH1/2 mutation, and 2 of 3 GBMs which showed IDH1/2 mutations were secondary GBMs. There was no significant difference in progression-free and overall survival between WHO grade II and III gliomas, possibly because all these tumors showed IDH1/2 mutations. In multivariate analysis, only the WHO grade (grade IV versus II and III combined) was significantly associated with increased risk of recurrence and death (P = 0.016 and 0.02).
CONCLUSION
The new integrated diagnosis provides a more meaningful classification, removing the considerable subjectivity that existed previously.
Topics: Adolescent; Adult; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Female; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Oligodendroglia; Oligodendroglioma; Prognosis; X-linked Nuclear Protein; Young Adult
PubMed: 30504574
DOI: 10.4103/0028-3886.246275 -
Archives of Pathology & Laboratory... Feb 2007Significant interobserver variability exists with respect to the diagnosis of oligodendroglial neoplasms, especially their distinction from astrocytoma and mixed... (Review)
Review
CONTEXT
Significant interobserver variability exists with respect to the diagnosis of oligodendroglial neoplasms, especially their distinction from astrocytoma and mixed oligoastrocytoma. Combined loss of the short arm of chromosome 1 and the long arm of chromosome 19 has been shown to be both relatively specific to oligodendroglioma and, when present, a marker of improved prognosis in patients with these tumors. In addition, 1p/19q loss has been shown to be a marker of "classic" oligodendroglial histology. These findings raise questions as to the role of 1p/19q testing in clinical practice, both as a prognostic marker and as a potential diagnostic marker among infiltrating glial neoplasms.
OBJECTIVE
This review discusses the issues raised above and tries to clarify the current status of 1p/19q evaluation in the diagnosis of oligodendroglioma.
DATA SOURCES
Sources for this review include recent literature as well as the experience of 3 practicing neuropathologists.
CONCLUSIONS
1p/19q status is an important marker in oligodendroglioma. Loss of 1p/19q is associated with classic oligodendroglioma histology as well as improved prognosis. The combined 1p/19q marker will continue to be a clinically useful marker of prognosis and could potentially be incorporated into diagnostic criteria in the future.
Topics: Biomarkers, Tumor; Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Humans; Oligodendroglioma; Prognosis
PubMed: 17284109
DOI: 10.5858/2007-131-242-CAOQLA -
Acta Neuropathologica Dec 2017Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the...
Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation in SETD2 (n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive with H3F3A K27M mutation (n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function including TP53 mutation (n = 9), PPM1D mutation (n = 2), and a novel type of PPM1D fusion (n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those with H3F3A mutations were categorized in the "RTK I (PDGFRA)" group, and those DCGs had a gene expression signature that was highly associated with PDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brain regions, promoter methylation of transcription factors genes associated with glial development showed a characteristic pattern presumably reflecting their tumor origin. Notably, SOX10, a key transcription factor associated with oligodendroglial differentiation and PDGFRA regulation, was up-regulated in both DCG and H3 K27M-mutant diffuse midline glioma, suggesting their developmental and biological commonality. In contrast, SOX10 was silenced by promoter methylation in most cerebral gliomas. These findings may suggest potential tailored targeted therapy for gliomas according to their brain region, in addition to providing molecular clues to identify the region-related cellular origin of DCGs.
Topics: Adult; Aged; Aged, 80 and over; Cerebellar Neoplasms; Cerebellum; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Glioma; Humans; Middle Aged
PubMed: 28852847
DOI: 10.1007/s00401-017-1771-1