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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 -
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 -
Journal of Comparative Pathology May 2020An 8-year-old Anglo-European gelding with progressive neurological signs was humanely destroyed and submitted for necropsy examination. The right parietal cortex was...
An 8-year-old Anglo-European gelding with progressive neurological signs was humanely destroyed and submitted for necropsy examination. The right parietal cortex was disrupted by a well-demarcated, intraparenchymal, 1.5 cm diameter, tan, homogeneous, dense mass. Microscopical examination was consistent with an astrocytoma, which was confirmed on the basis of strong immunohistochemical labelling for glial fibrillary acidic protein. The neoplastic population lacked immunolabelling for oligodendrocyte transcription factor 2. Labelling for ionized calcium binding adaptor molecule 1 highlighted large numbers of reactive microglia throughout the proliferation and in the adjacent neuroparenchyma. While rare, primary brain tumours should be considered as a differential in horses presenting with progressive neurological signs.
Topics: Animals; Astrocytoma; Autopsy; Brain Neoplasms; Glial Fibrillary Acidic Protein; Horse Diseases; Horses; Immunohistochemistry; Male; Oligodendrocyte Transcription Factor 2
PubMed: 32505235
DOI: 10.1016/j.jcpa.2020.03.009 -
Acta Neuropathologica Communications Jun 2021Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations...
Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.
Topics: Adolescent; Adult; Aged; Astrocytoma; Child; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Molecular Diagnostic Techniques; Retrospective Studies; Spinal Cord Neoplasms; Young Adult
PubMed: 34193285
DOI: 10.1186/s40478-021-01222-6 -
Clinical Neuropathology 2017Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the
CDKN2A tumor suppressor gene...Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history.
Familial melanoma-astrocytoma syndrome is a tumor predisposition syndrome caused by inactivating germline alteration of the
CDKN2A tumor suppressor gene on chromosome 9p21. While some families with germlineCDKN2A mutations are prone to development of just melanomas, other families develop both melanomas, astrocytomas, and occasionally other nervous-system neoplasms including peripheral nerve sheath tumors and meningiomas. The histologic spectrum of the astrocytomas that arise as part of this syndrome is not well described, nor are the additional genetic alterations that drive these astrocytomas apart from the germlineCDKN2A inactivation. Herein, we report the case of a young man with synchronous development of a pleomorphic xanthoastrocytoma, diffuse astrocytoma, and paraspinal mass radiographically consistent with a peripheral nerve sheath tumor. His paternal family history is significant for melanoma, glioblastoma, and oral squamous cell carcinoma. Genomic profiling revealed that he harbors a heterozygous deletion in the germline of chromosome 9p21.3 encompassing theCDKN2A andCDKN2B tumor suppressor genes. Both the pleomorphic xanthoastrocytoma and diffuse astrocytoma were found to have homozygous deletion ofCDKN2A/B due to somatic loss of the other copy of chromosome 9p containing the remaining intact alleles. Additional somatic alterations includedBRAF p.V600E mutation in the pleomorphic xanthoastrocytoma andPTPN11 ,ATRX , andNF1 mutations in the diffuse astrocytoma. The presence of germlineCDKN2A/B inactivation together with the presence of multiple anatomically, histologically, and genetically distinct astrocytic neoplasms, both with accompanying somatic loss of heterozygosity for theCDKN2A/B deletion, led to a diagnosis of familial melanoma-astrocytoma syndrome. This remarkable case illustrates the histologic and genetic diversity that astrocytomas arising as part of this rare glioma predisposition syndrome can demonstrate. .Topics: Astrocytoma; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p18; Humans; Male; Melanoma; Nervous System Neoplasms; Pedigree; Young Adult
PubMed: 28699883
DOI: 10.5414/NP301022 -
Science Translational Medicine Aug 2016Genomic markers provide unbiased information that is increasingly being used to enhance traditional histopathology approaches for classification of cancer samples. (Review)
Review
Genomic markers provide unbiased information that is increasingly being used to enhance traditional histopathology approaches for classification of cancer samples.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Glioblastoma; Glioma; Humans; Oligodendroglioma
PubMed: 27488893
DOI: 10.1126/scitranslmed.aah4740 -
Journal of Veterinary Diagnostic... Jul 2019Gliomas are common primary central nervous system neoplasms of dogs and cats, but atypical glioma subtypes are rare. Herein we report an angiocentric astrocytoma in a...
Gliomas are common primary central nervous system neoplasms of dogs and cats, but atypical glioma subtypes are rare. Herein we report an angiocentric astrocytoma in a 15-y-old spayed female domestic shorthaired cat that was euthanized after therapy-resistant seizures. Gross anatomic changes consisted of swelling of the rostral leptomeninges over the olfactory bulbs and rostral telencephalon. Histologically, polygonal-to-elongate atypical neoplastic cells were arranged along perivascular spaces within these areas. Neoplastic cells were positive for glial fibrillary acidic protein, S100 protein, and vimentin. Ultrastructurally, round-to-elongate neoplastic cells emitting long processes with aggregates of intermediary filaments expanded and occupied the spaces between the vascular basement membrane and the glia limitans; nuclei had marginal and central heterochromatin. Tight junctions connected the plasma membrane of neighboring cells. The cell morphology, immunohistochemistry, and ultrastructural findings were consistent with an astrocytoma; the exclusive perivascular arrangement of neoplastic cells with no parenchymal mass warranted the diagnosis of angiocentric astrocytoma.
Topics: Animals; Astrocytoma; Brain; Brain Neoplasms; Cat Diseases; Cats; Female; Glial Fibrillary Acidic Protein; S100 Proteins; Seizures; Vimentin
PubMed: 31018782
DOI: 10.1177/1040638719847239 -
Survey of Ophthalmology 2015Although the introduction of intravitreal anti-vascular endothelial growth factor drugs reduced the indications for photodynamic therapy in ophthalmology, it may still... (Meta-Analysis)
Meta-Analysis Review
Although the introduction of intravitreal anti-vascular endothelial growth factor drugs reduced the indications for photodynamic therapy in ophthalmology, it may still be used in various ocular tumors. Although many studies have shown that photodynamic therapy is effective in ocular tumors, the literature consists of case reports and series. In this review, we systematically performed a meta-analysis for the use of photodynamic therapy in circumscribed choroidal hemangioma, diffuse choroidal hemangioma, retinal capillary hemangioma, von Hippel-Lindau angiomatosis, choroidal melanoma, retinal astrocytoma, retinoblastoma, eyelid tumors, conjunctival tumors, and choroidal metastasis.
Topics: Astrocytoma; Choroid Neoplasms; Conjunctival Neoplasms; Eye Neoplasms; Eyelid Neoplasms; Hemangioma; Hemangioma, Capillary; Humans; Melanoma; Photochemotherapy; Photosensitizing Agents; Retinal Neoplasms; Retinoblastoma
PubMed: 26079736
DOI: 10.1016/j.survophthal.2015.05.004 -
Radiation Oncology (London, England) May 2022We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and...
BACKGROUND
We sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and 2 mutation status in patients with radiation-induced glioma (RIG).
METHODS
We retrospectively reviewed the clinical characteristics and treatment outcomes of 11 patients with high-grade glioma who satisfied Cahan's criteria for RIG in our database during 2001-2021. IDH 1/2 mutations were analyzed by Sanger sequencing and/or pyrosequencing.
RESULTS
The RIGs included glioblastoma with IDH 1/2 wild-type (n = 7), glioblastoma not otherwise specified (n = 2), anaplastic astrocytoma with IDH1/2 wild-type (n = 1), and anaplastic astrocytoma not otherwise specified (n = 1). The median period from primary disease and RIG diagnosis was 17 years (range: 9-30 years). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and survival times were 11.3 and 28.3 months. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n = 5) tended to be longer than that of patients that received chemotherapy alone (n = 6) (17.0 vs 8.1 months). However, the median survival time was similar (29.6 vs 27.4 months). Local recurrence was observed in 5 patients treated with chemotherapy alone, whereas in 2 patients among 4 patients treated with reirradiation and chemotherapy. None of the patients developed radiation necrosis. In one case, the primary tumor was diffuse astrocytoma with IDH2 mutant, and the secondary tumor was glioblastoma with IDH 1/2 wild-type. Based on the difference of IDH2 mutation status, the secondary tumor with IDH 1/2 wild-type was diagnosed as a de novo tumor that was related to the previous radiation therapy.
CONCLUSIONS
RIG can occur beyond 20 years after successfully treating the primary disease using radiotherapy; thus, cancer survivors should be informed of the long-term risk of developing RIG and the need for timely neuroimaging evaluation. Reirradiation combined with chemotherapy appears to be feasible and has favorable outcomes. Determining the IDH1/2 mutational status is useful to establish RIG diagnosis when the primary tumor is glioma.
Topics: Astrocytoma; Brain Neoplasms; Glioblastoma; Glioma; Humans; Isocitrate Dehydrogenase; Re-Irradiation; Retrospective Studies
PubMed: 35505351
DOI: 10.1186/s13014-022-02054-x -
Applied Immunohistochemistry &...High podoplanin (PDPN) expression correlates with poor prognosis in various cancers. However, the expression and clinical value of PDPN in glioma are unclear. In this...
High podoplanin (PDPN) expression correlates with poor prognosis in various cancers. However, the expression and clinical value of PDPN in glioma are unclear. In this study, PDPN expression was compared in 227 glioma tissues and 22 paired non-neoplastic tissues, and its association with prognostic factors was statistically analyzed. The effect of PDPN knockdown on the proliferation ability of glioma cells (U87MG and U118MG cell lines) was assessed along with the underlying molecular mechanism. Overexpression of PDPN was observed in the majority of glioma tissues compared with the expression in normal tissues. PDPN overexpression was positively correlated with IDH wild-type status, TERT promoter mutation status, and ATRX retention status, and was negatively correlated with 1p/19q codeletion status. The expression level of PDPN was positively correlated with the glioma grade in the diffuse astrocytoma, IDH wild-type. High PDPN expression was also negatively correlated with survival in astrocytoma patients with IDH mutation or wild-type and in glioblastoma patients with IDH wild-type. Grade, radiochemotherapy, and PDPN overexpression emerged as independent indicators for a poor prognosis of glioma patients. PDPN knockdown suppressed proliferation and reduced p-Akt and p-mTOR protein expression in glioma cells. PDPN is a potential biomarker or therapeutic target for glioma that is closely associated with tumor grade and poor prognosis, which may play a role in enhancing cell proliferation via Akt/mTOR signaling.
Topics: Humans; Astrocytoma; Brain Neoplasms; Glioma; Isocitrate Dehydrogenase; Mutation; Proto-Oncogene Proteins c-akt
PubMed: 37093708
DOI: 10.1097/PAI.0000000000001120