Molecular classification of glioblastoma based on immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins

Jankowska, Sylwia; Lewandowska, Magdalena; Masztalewicz, Marta; Sagan, Leszek; Nowacki, Przemysław; Urasińska, Elżbieta

doi:10.5114/pjp.2021.106439

Cited by 7 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alterations captured by NGS in two patients were consistent with molecular alterations commonly observed in GBM, including EGFR amplification and mutations in PTEN and NF1 [45][46][47][48]. EGFR amplification has been observed in 57% of GBM and is associated with enhanced tumor cell angiogenesis [49].…”

Section: Discussionsupporting

confidence: 67%

Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series

Parker,

Kalluri,

Materi

et al. 2023

IJMS

View full text Add to dashboard Cite

While the central nervous system (CNS) tumor classification has increasingly incorporated molecular parameters, there is a paucity of literature reporting molecular alterations found in intraventricular glioblastoma (IVGBM), which are rare. We present a case series of nine IVGBMs, including molecular alterations found in standardized next-generation sequencing (NGS). We queried the clinical charts, operative notes, pathology reports, and radiographic images of nine patients with histologically confirmed IVGBM treated at our institution (1995–2021). Routine NGS was performed on resected tumor tissue of two patients. In this retrospective case series of nine patients (22% female, median (range) age: 64.3 (36–85) years), the most common tumor locations were the atrium of the right lateral ventricle (33%) and the septum pellucidum (33%). Five patients had preoperative hydrocephalus, which was managed with intraoperative external ventricular drains in three patients and ventriculoperitoneal shunts in one patient. Hydrocephalus was managed with subtotal resection of a fourth ventricular IVGBM in one patient. The most common surgical approach was transcortical intraventricular (56%). Gross total resection was achieved in two patients, subtotal resection was achieved in six patients, and one patient received a biopsy only. Immunohistochemistry for IDH1 R132H mutant protein was performed in four cases and was negative in all four. Genetic alterations common in glioblastoma, IDH-wildtype, were seen in two cases with available NGS data, including EGFR gene amplification, TERT promoter mutation, PTEN mutation, trisomy of chromosome 7, and monosomy of chromosome 10. Following surgical resection, four patients received adjuvant chemoradiation. Median survival among our cohort was 4.7 months (IQR: 0.9–5.8 months). Management of IVGBM is particularly challenging due to their anatomical location, presentation with obstructive hydrocephalus, and fast growth, necessitating prompt intervention. Additional studies are needed to better understand the genetic landscape of IVGBM compared to parenchymal glioblastoma and may further elucidate the unique pathophysiology of these rare tumors.

show abstract

Section: Discussionsupporting

confidence: 67%

Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series

Parker,

Kalluri,

Materi

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…CL and PN subtypes had a profile characteristic of highly proliferative cells [20,114] and indeed WG4, WG9, WG14 cells had a high proliferation index. Transcriptional analysis is not routinely feasible in clinical setting, therefore a simplified method based on the IHC expression of some proteins was proposed [75,76,115,116]. In this study, we evaluated seven proteins (EGFR, PDGFRa, IDH1 R132H , TP53, CHI3L1/YKL40, CD44 and phSTAT3) as molecular markers for GBM subtyping.…”

Section: Discussionmentioning

confidence: 99%

Exploring Responses of Glioblastoma Patient-Derived Cell Cultures to Drugs Reveals New Therapeutic Opportunities

Ciechomska¹,

Wojnicki²,

Wojtaś³

et al. 2023

Preprint

View full text Add to dashboard Cite

Glioblastomas (GBM) are most common, primary brain tumors in adults. Despite advances in neurosurgery, radio- and chemotherapy, the median survival of GBM patients is 15 months. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and molecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have established 13 GBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNAseq, immunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1R132H, TP53 and PDGFRα), classical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), as well as expression of pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, β-Tubulin III) markers revealed the striking inter-tumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-CADHERIN and CD44 at mRNA/protein levels suggested increased epithelial to mesenchymal transition (EMT) in most studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-derived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated cultures the strongest accumulation of apoptotic markers: caspase 7 and PARP were found in WG4 cells with methylated MGMT suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-derived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream signaling pathways. AG1478 caused decreased levels of phospho-STAT3, thus inhibition of active STAT3 augmented antitumor effects of DOX and TMZ in cells with methylated and intermediate status of MGMT. Altogether, our findings show that GBM-derived cell cultures mimic the considerable tumor heterogeneity and identifying patient-specific signaling vulnerabilities can assist in overcoming therapy resistance, by providing personalized combinatorial treatment recommendations.

show abstract

“…Immunohistochemical (IHC) staining of subtype-specific marker genes (EGFR, PDGFRA, NF1, IDH1, P53, CD44, MERTK, and PTEN) can indicate the degree of malignancy in patients with glioma and aid in predicting their clinical prognosis. Likewise, simple IHC staining of GBM markers can help distinguish tumor subtypes in clinical samples and may facilitate analysis of large sample sizes [16][17][18] . Furthermore, 2 independent studies have reported the development of radiomics-based assays to better predict molecular subtypes and prognosis in patients with GBM 19,20 .…”

Section: Molecular Classification Of Gbmmentioning

confidence: 99%

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

Xu,

Hou,

et al. 2024

Cancer Biol Med

View full text Add to dashboard Cite

Among central nervous system-associated malignancies, glioblastoma (GBM) is the most common and has the highest mortality rate. The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide. In precision medicine, research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity, as well as the refractory nature of GBM toward therapy. Deep understanding of the different molecular expression patterns of GBM subtypes is critical. Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes. The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors. These subtypes also exhibit high plasticity in their regulatory pathways, oncogene expression, tumor microenvironment alterations, and differential responses to standard therapy. Herein, we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype. Furthermore, we review the mesenchymal transition mechanisms of GBM under various regulators.

show abstract

Molecular classification of glioblastoma based on immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins

Cited by 7 publications

References 27 publications

Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series

Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series

Exploring Responses of Glioblastoma Patient-Derived Cell Cultures to Drugs Reveals New Therapeutic Opportunities

Comprehensive understanding of glioblastoma molecular phenotypes: classification, characteristics, and transition

Contact Info

Product

Resources

About