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AJNR. American Journal of Neuroradiology Aug 2018Anaplastic pleomorphic xanthoastrocytoma, which has been recently defined as a distinct entity in the 2016 World Health Organization classification, may exhibit...
BACKGROUND AND PURPOSE
Anaplastic pleomorphic xanthoastrocytoma, which has been recently defined as a distinct entity in the 2016 World Health Organization classification, may exhibit aggressive clinical behavior and relatively worse prognosis than pleomorphic xanthoastrocytoma. This study aimed to investigate whether there were any differences in MR imaging characteristics between these 2 tumors.
MATERIALS AND METHODS
This retrospective study included 9 patients with anaplastic pleomorphic xanthoastrocytoma and 10 patients with pleomorphic xanthoastrocytoma who underwent MR imaging before an operation. DWI was performed in 17 patients (8 with anaplastic pleomorphic xanthoastrocytoma, 9 with pleomorphic xanthoastrocytoma); and DSC-PWI, in 9 patients (5 with anaplastic pleomorphic xanthoastrocytoma, 4 with pleomorphic xanthoastrocytoma). Demographics, conventional imaging characteristics (location, size, cystic degeneration, enhancement, peritumoral edema, and leptomeningeal contact), minimum relative ADC ratio, and maximum relative CBV ratio were evaluated between the anaplastic pleomorphic xanthoastrocytoma and pleomorphic xanthoastrocytoma groups.
RESULTS
Anaplastic pleomorphic xanthoastrocytoma was more likely to demonstrate high-grade features than pleomorphic xanthoastrocytoma, including greater maximum tumor diameter (4.7 ± 0.6 cm versus 3.1 ± 1.1 cm, = .001), more frequent heterogeneous contrast enhancement of solid portions (88.9% versus 20.0%, = .01), more obvious peritumoral edema (2.3 ± 0.9 cm versus 1.0 ± 0.9 cm, = .008), lower minimum relative ADC on DWI (1.0 ± 0.2 versus 1.5 ± 0.4, = .008), and higher maximum relative CBV on DSC-PWI (2.6 ± 0.8 versus 1.6 ± 0.2, = .036).
CONCLUSIONS
Anaplastic pleomorphic xanthoastrocytomas often have more aggressive MR imaging features mimicking high-grade astrocytomas than pleomorphic xanthoastrocytomas. DWI and DSC-PWI might be useful in the characterization and differentiation of anaplastic pleomorphic xanthoastrocytoma and pleomorphic xanthoastrocytoma.
Topics: Adult; Astrocytoma; Brain Neoplasms; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Retrospective Studies
PubMed: 29903923
DOI: 10.3174/ajnr.A5701 -
Pathology Oncology Research : POR Oct 2012The role of insulin-like growth factors and their regulatory proteins (IGFBP isoforms) in gliomas, particularly glioblastoma, has been a subject of active research in...
The role of insulin-like growth factors and their regulatory proteins (IGFBP isoforms) in gliomas, particularly glioblastoma, has been a subject of active research in recent years. There is paucity of literature on their expression and impact on clinical outcome in anaplastic astrocytomas. To evaluate the expression patterns of IGFBP isoforms in anaplastic astrocytoma and correlate with clinical outcome, a retrospective study of 53 adult patients operated for supratentorial lobar anaplastic astrocytoma was performed. The protein expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7), was studied by immunohistochemistry on all samples. The patients were followed up and outcome was documented. The median age at presentation in the present study was 35 years. The pattern of staining was intra cytoplasmic, homogenous and diffuse for IGFBP-2, -3 and -5 and granular for IGFBP-7. IGFBP-2 expression was significantly low in anaplastic astrocytoma as compared to other isoforms (P < 0.001). IGFBP-3 expression was higher than the other isoforms. However, its' expression correlated with favorable overall survival and demonstrated a trend towards significance on univariate analysis. The present study is the first of its kind to describe comprehensively the pattern of expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7) in anaplastic astrocytomas. IGFBP-2 and IGFBP-3 expression patterns and correlation to prognosis were distinct in anaplastic astrocytoma patients, contradictory to what has been reported in glioblastoma, thus giving further evidence that anaplastic astrocytomas are molecularly distinct from glioblastoma.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Astrocytoma; Brain Neoplasms; Female; Humans; Immunohistochemistry; Insulin-Like Growth Factor Binding Proteins; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Protein Isoforms; Retrospective Studies
PubMed: 22547392
DOI: 10.1007/s12253-012-9526-8 -
Asian Pacific Journal of Cancer... Sep 2022This study evaluated the differences between IDH1-R132H and CD133 expression in different categories of astrocytoma.
OBJECTIVE
This study evaluated the differences between IDH1-R132H and CD133 expression in different categories of astrocytoma.
MATERIAL AND METHODS
This study used a cross-sectional design. Sixty-seven paraffin embedded block of Diffuse Astrocytoma (DA), Anaplastic Astrocytoma (AA) and Glioblastoma (GB) were assessed using using the monoclonal antibody IDH1-R132H and Rabbit polyclonal antibody CD133.
RESULTS
It was found that there was a significant relationship between the expression of IDH1-R132H and CD133 in DA, AA and GB (p<0.001). Astrocytoma with IDH-mutant molecular status will express more markers of cancer stem cell CD133 than IDH-wildtype.
CONCLUSION
The IDH1-R132H and CD133 can provide predictive value on treatment success, disease prognosis, recurrence and can be considered as target combination therapy with chemotherapy.
Topics: Animals; Antibodies, Monoclonal; Astrocytoma; Biomarkers; Brain Neoplasms; Cross-Sectional Studies; Glioblastoma; Isocitrate Dehydrogenase; Mutation; Neoplastic Stem Cells; Rabbits
PubMed: 36172668
DOI: 10.31557/APJCP.2022.23.9.3051 -
Oncotarget Apr 2017Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and...
BACKGROUND
Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been shown to increase cellular proliferation and tumorigenesis in many types of cancer; however, previous reports have not described a correlation between clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to elucidate the clinical role of Fli-1 in astrocytoma.
RESULTS
High-level of Fli-1 protein expression was significantly association with World Health Organization (WHO) high grade and poor prognosis. A multivariate analysis revealed that the WHO grade and Fli-1 protein expression were independent factor of prognostic factors of patients with astrocytoma. In addition, Fli-1 silencing inhibited proliferation, migration, and invasion and led to the downregulation of Ki-67, VEGF, and cyclin D1 expression in the astrocytoma cells.
MATERIALS AND METHODS
Fli-1 protein expression in astrocytoma tissue samples were detected via immunohistochemistry, and potential correlations between clinical parameters and Fli-1 expression were assessed in patients with astrocytoma. Additionally, proliferation, invasion, and migration assays of astrocytoma cell lines were conducted to evaluate the effects of short interfering RNA (siRNA) on these processes; in addition, these cells were subjected to western blotting to detect the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1.
CONCLUSION
Fli-1 shows promise as a potential prognostic biomarker and therapeutic molecular target for astrocytoma patients.
Topics: Astrocytoma; Cell Culture Techniques; Cell Line, Tumor; Female; Humans; Male; Microfilament Proteins; Prognosis; Receptors, Cytoplasmic and Nuclear; Survival Analysis; Trans-Activators; Transfection
PubMed: 28418872
DOI: 10.18632/oncotarget.16303 -
Survival, Prognostic Factors, and Volumetric Analysis of Extent of Resection for Anaplastic Gliomas.Cancer Research and Treatment Oct 2020The aim of this study is to evaluate the survival rate and prognostic factors of anaplastic gliomas according to the 2016 World Health Organization classification,...
PURPOSE
The aim of this study is to evaluate the survival rate and prognostic factors of anaplastic gliomas according to the 2016 World Health Organization classification, including extent of resection (EOR) as measured by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) and the T2-weighted MRI.
MATERIALS AND METHODS
The records of 113 patients with anaplastic glioma who were newly diagnosed at our institute between 2000 and 2013 were retrospectively reviewed. There were 62 cases (54.9%) of anaplastic astrocytoma, isocitrate dehydrogenase (IDH) wild-type (AAw), 18 cases (16.0%) of anaplastic astrocytoma, IDH-mutant, and 33 cases (29.2%) of anaplastic oligodendroglioma, IDH-mutant and 1p/19q-codeleted.
RESULTS
The median overall survival (OS) was 48.4 months in the whole anaplastic glioma group and 21.5 months in AAw group. In multivariate analysis, age, preoperative Karnofsky Performance Scale score, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, postoperative tumor volume, and EOR measured from the T2 MRI sequence were significant prognostic factors. The EOR cut-off point for OS measured in contrast-enhanced T1-weighted MRI and T2-weighted MRI were 99.96% and 85.64%, respectively.
CONCLUSION
We found that complete resection of the contrast-enhanced portion (99.96%) and more than 85.64% resection of the non-enhanced portion of the tumor have prognostic impacts on patient survival from anaplastic glioma.
Topics: Adolescent; Adult; Astrocytoma; Brain; Brain Neoplasms; Female; Humans; Isocitrate Dehydrogenase; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Neurosurgical Procedures; Oligodendroglioma; Prognosis; Progression-Free Survival; Retrospective Studies; Survival Rate; Tumor Burden
PubMed: 32324987
DOI: 10.4143/crt.2020.057 -
The Oncologist May 2021IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine...
Radiotherapy Plus Procarbazine, Lomustine, and Vincristine Versus Radiotherapy Plus Temozolomide for IDH-Mutant Anaplastic Astrocytoma: A Retrospective Multicenter Analysis of the French POLA Cohort.
BACKGROUND
IDH-mutant anaplastic astrocytomas (AAs) are chemosensitive tumors for which the best choice of adjuvant chemotherapy between procarbazine, lomustine, and vincristine (PCV) or temozolomide (TMZ) after radiotherapy (RT) remains unclear.
METHODS
In a large cohort of patients with histologically proven 2016 World Health Organization classification AA with IDH1/2 mutations included in the French national POLA cohort (n = 355), the primary objective was to compare progression-free survival (PFS) between the two treatment regimens (n = 311). Secondary endpoints were overall survival (OS), progression type, pseudoprogression rate, and toxicity.
RESULTS
The 4-year PFS in the RT + PCV arm was 70.8% versus 53.5% in the RT + TMZ arm, with a hazard ratio (HR) of 0.58 (95% confidence interval [CI], 0.38-0.87; p = .0074) in univariable analysis and 0.63 (95% CI, 0.41-0.97; p = .0348) in multivariable analysis. The 4-year OS in the RT + PCV arm was 84.3% versus 76.6% in the RT + TMZ arm, with an HR of 0.57 (95% CI, 0.30-1.05; p = .0675) in univariable analysis. Toxicity was significantly higher in the RT + PCV arm with more grade ≥3 toxicity (46.7% vs. 8.6%, p < .0001).
CONCLUSION
RT + PCV significantly improved PFS compared with RT + TMZ for IDH-mutant AA. However, RT + TMZ was better tolerated.
IMPLICATIONS FOR PRACTICE
In the absence of fully conducted randomized trials comparing procarbazine, lomustine, and vincristine (PCV) with temozolomide (TMZ) in adjuvant treatment after radiotherapy (RT) for the management of IDH-mutant anaplastic astrocytoma (AA) and a similar level of evidence, these two chemotherapies are both equally recommended in international guidelines. This study in a national cohort of IDH-mutant AA defined according the 2016 World Health Organization (WHO) classification shows for the first time that the RT + PCV regimen significantly improves progression-free survival in comparison with the RT + TMZ regimen. Even if at the time of analysis the difference in overall survival was not significant, this result provides new evidence for the debate about the chemotherapy regimen to prescribe in adjuvant treatment to RT for WHO 2016 IDH-mutant AA.
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Humans; Lomustine; Procarbazine; Retrospective Studies; Temozolomide; Vincristine
PubMed: 33524191
DOI: 10.1002/onco.13701 -
Journal of Cancer Research and... 2022Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven...
BACKGROUND
Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven equivocal. The present study aims to evaluate the risk variables, indicating that LGA gradually differentiates to malignant astrocytoma.
METHODS
Retrospective cohort analysis of LGA patients was performed. Both univariate and multivariate studies were used to discover variables connected to MT using the Cox regression method. As a result, the cumulative incidence of MT for each covariate survival curve was built after the final model.
RESULTS
In the current study, 115 individuals with LGA were included in the analysis, and MT was found in 16.5% of cases. In the case of MT, 68.4% of patients progressed to glioblastoma, whereas 31.6% progressed to anaplastic astrocytoma. Significant factors included supratentorial tumor (hazard ratio (HR) 3.41, 95% CI 1.18-12.10), midline shift > 5 mm (HR 7.15, 95% CI 2.28-34.33), and non-total resection as follows: subtotal resection (HR 5.09, 95% CI 0.07-24.02), partial resection (HR 1.61, 95% CI 1.09-24.11), and biopsy (HR 2.80, 95% CI 1.18-32.52).
CONCLUSION
In individuals with LGA, MT dramatically altered the disease's natural history to a poor prognosis. The present study's analysis of the clinical features of patients indicated supratentorial LGA, a midline shift greater than 5 mm, and the degree of resection as risk factors for MT. The more extensive the resection, the greater the reduction in tumor load and MT. In addition, more molecular study is necessary to elucidate the pathophysiology of MT.
Topics: Humans; Retrospective Studies; Brain Neoplasms; Astrocytoma; Glioblastoma; Cell Transformation, Neoplastic
PubMed: 36412420
DOI: 10.4103/jcrt.JCRT_1469_20 -
Current Oncology (Toronto, Ont.) Feb 2023Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO...
PURPOSE
Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs.
METHODS
Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%).
RESULTS
Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; = 0.0005) and all mutation sites were C228T. The cases without mutation or with necrosis in grade 3 PXA had a poor prognosis ( = 0.01).
CONCLUSION
These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and mutation play an important role in the prognosis of grade 3 PXA.
Topics: Child; Young Adult; Humans; Proto-Oncogene Proteins B-raf; Astrocytoma; Mutation; Prognosis
PubMed: 36826144
DOI: 10.3390/curroncol30020183 -
Acta Neuropathologica Communications Aug 2020Intramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions...
Intramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions and the H3F3A p.K27M mutation have been described in low-grade (LG) and high-grade (HG) IMAs, respectively. In the present study, we collected clinico-radiological data and performed targeted next-generation sequencing for 61 IMAs (26 grade I pilocytic, 17 grade II diffuse, 3 LG, 3 grade III and 12 grade IV) to identify KIAA1549-BRAF fusions and mutations in 33 genes commonly implicated in gliomas and the 1p/19q regions. One hundred seventeen brain astrocytomas were analyzed for comparison. While we did not observe a difference in clinico-radiological features between LG and HG IMAs, we observed significantly different overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the tumor grade was associated with better OS while EFS was strongly impacted by tumor grade and surgery, with higher rates of disease progression in cases in which only biopsy could be performed. For LG IMAs, EFS was only impacted by surgery and not by grade. The most common mutations found in IMAs involved TP53, H3F3A p.K27M and ATRX. As in the brain, grade I pilocytic IMAs frequently harbored KIAA1549-BRAF fusions but with different fusion types. Non-canonical IDH mutations were observed in only 2 grade II diffuse IMAs. No EGFR or TERT promoter alterations were found in IDH wild-type grade II diffuse IMAs. These latter tumors seem to have a good prognosis, and only 2 cases underwent anaplastic evolution. All of the HG IMAs presented at least one molecular alteration, with the most frequent one being the H3F3A p.K27M mutation. The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.
Topics: Adolescent; Adult; Aged; Astrocytoma; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Progression-Free Survival; Spinal Cord Neoplasms; Young Adult
PubMed: 32771057
DOI: 10.1186/s40478-020-00962-1 -
Neuro-oncology Apr 1999Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth... (Review)
Review
Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis.
Topics: Alleles; Apoptosis; Astrocytoma; Brain Neoplasms; Cell Cycle; Cell Division; Cell Transformation, Neoplastic; Cyclin D; Cyclins; DNA Repair; Disease Progression; ErbB Receptors; Gene Amplification; Gene Expression Regulation, Neoplastic; Genes, Retinoblastoma; Genes, Tumor Suppressor; Genes, p16; Genes, p53; Glioblastoma; Humans; Loss of Heterozygosity; Mutation; PTEN Phosphohydrolase; Phosphoric Monoester Hydrolases; Prognosis; Tumor Suppressor Protein p53; Tumor Suppressor Proteins
PubMed: 11550308
DOI: 10.1093/neuonc/1.2.124