A phase II trial of temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: An AINO (Italian Association for Neuro-Oncology) study.

2026 Background: The efficacy of dose-dense temozolomide (TMZ, 1 week on/1 week off ) in grade II gliomas is not well known and could depend on the molecular subtype. Methods: Between 2006 and 2010 a single arm phase II study on 60 patients with grade II oligodendroglial tumors was performed. Inclusion criteria were as follows: 1) age ≥ 18 years; 2) KPS ≥ 70; 3) biopsy-proven grade II oligodendroglioma or oligoastrocytoma ; 4) a measurable residual tumor after surgery. The primary endpoint was tumor response on MRI according to RANO criteria, while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and seizure control. Most patients (65%) had seizures. Molecular factors (IDH 1-2 mutations, 1p19q codeletion, MGMT methylation) were available in 49/60 patients (81.7%). The median number of cycles was 11 (2-18). Median follow up was 64 months (7-112). Results: Response rate was PR in 21/60 (35%) patients, minor PR (mPR) in 14/60 (23%), SD in 21/60 (35%) and PD in 4/60 (7%). Most patients achieved the best tumor response within 6 months after the start of TMZ. Among patients with mPR and PR, 15/49 (30.6%) were IDH1-2 mutated with a PFS of 71.4% at 36 months and 28.6% at 60 months with a median value of 46 months while 11/49 (22.4%) were IDH 1-2 wild-type with a PFS of 45.8% at 36 months and 25% at 60 months with a median value of 34 months. OS was 90.5% at 36 months and 66.7% at 60 months with a median value of 76 months in the IDH1-2 mutated/1p19q codeleted subgroup, while OS was 66.7% at 36 months and 50% at 60 months with a median value of 60 months in the IDH1-2 wild-type subgroup. Responses were higher in MGMT methylated patients. Seizure improvement was achieved in 29/34 patients (85%): 17/33 (52%) patients at 12 months and 18/29 (62.1%) at 24 months were seizure-free. Time to maximal seizure response was earlier than that observed on MRI (3 vs 6 months). Conclusions: Dose-dense TMZ has shown a significant activity in terms of tumor and seizure control, especially in IDH1-2 mutated/1p19q codeleted patients. Seizure reduction could represent an early indicator of response to chemotherapy and maybe predict the duration of response. Clinical trial information: 2007-000386-38.

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Quantitative analysis of 06-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with low-grade gliomas

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2069 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2069-2069

Author(s):

A. F. Ochsenbein ◽

A. D. Schubert ◽

E. Vassella ◽

L. Mariani

Keyword(s):

Promoter Methylation ◽

Tumor Response ◽

Methylation Status ◽

Mgmt Promoter Methylation ◽

Low Grade ◽

Who Grade ◽

Low Grade Gliomas ◽

Response To Chemotherapy ◽

Mgmt Promoter ◽

Grade Ii

2069 Background: Loss of heterozygosity (LOH) on the chromosomes 1p and 19q is associated with sensitivity to alkylating agents like temozolomide (TMZ) in patients with low-grade gliomas; whether methylation of the MGMT-promoter, a predictive factor in glioblastoma patients, also correlates with tumor response to TMZ in low-grade gliomas is unclear. Methods: We performed a retrospective analysis of patients with histologically verified low-grade gliomas (WHO Grade II) who were treated with TMZ for tumor progression at our hospital between November 1999 and November 2007. Objective tumor response was assessed by MRI at 6-month intervals. LOH of microsatellite markers on chromosomes 1p and 19q was determined by polymerase chain reaction (PCR) amplification of the matched pairs of blood and tumor DNA. A methylation-specific, primer extension based PCR method was developed to quanitatively assess the MGMT methylation status in the tumour tissue. Results: Twenty-two patients with a median age of 53 years (range 27–72) were included in the study; 59% were male. Seven patients had prior surgical resection of the tumor. Histological classification revealed 10 oligodendrogliomas, 7 oligoastrocytomas, and 5 astrocytomas. All patients were treated with TMZ 200mg/m2 day1–5 in a 4 wk cycle. Grade 3–4 hematological toxicity occurred in 32% of the patients (9% leucopenia, 23% thrombocytopenia). The progression free survival was 32 months. Combined LOH 1p and 19q was found in 14 pts; 1 patient had LOH 1p alone and 1 patient LOH 19q alone. The LOH status could not be determined in two patients and was normal in the remaining four. MGMT promoter methylation was detectable in 20 pts by conventional PCR and quantitative analysis revealed a methylation status between 12%-100%. The volumetric response to chemotherapy analyzed after 6 months by MRI correlated with the level of MGMT promoter methylation (p = 0.012). Conclusions: Quantitative methylation-specific PCR of the MGMT promoter correlates with radiological response to chemotherapy with temozolomide in WHO grade II gliomas. No significant financial relationships to disclose.

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Phase II trial of dose-dense temozolomide as initial treatment for progressive low-grade oligodendroglial tumors: A multicentric study of the Italian Association of Neuro-Oncology (AINO).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2037 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2037-2037 ◽

Cited By ~ 3

Author(s):

Roberta Ruda ◽

Luca Bertero ◽

Elisa Trevisan ◽

Andrea Pace ◽

Carmine Maria Carapella ◽

...

Keyword(s):

Phase Ii ◽

Clinical Benefit ◽

Karnofsky Performance Status ◽

Epileptic Seizures ◽

Low Grade ◽

Who Grade ◽

Multicentric Study ◽

Oligodendroglial Tumors ◽

Dose Dense ◽

The Impact

2037 Background: Standard temozolomide has been shown to be active in progressive low grade gliomas after surgery, whereas few data are available on the impact of dose dense regimens. Thus, we developed a phase II single arm multicenter study to evaluate the efficacy and toxicity of a regimen of dose dense temozolomide in progressive low grade oligodendroglial tumors. Methods: The inclusion criteria of the study were as follows: 1)biopsy-proven supratentorial WHO grade II oligodendroglioma and oligoastrocytoma; 2)progressive disease, clinically (epileptic seizures)or radiologically; 3)measurable disease on MRI (at least 1 cm); 4)age ≥18 years; 5)Karnofsky Performance Status ≥70. Temozolomide was administered at 150mg/m2 1 week on/1 week off up to a maximum of 18 cycles or unacceptable toxicity. The primary end-point was response rate (RR) according to RANO criteria, whereas secondary end-points were clinical benefit in terms of reduction of epileptic seizures ≥50%, progression-free survival (PFS), quality of life and toxicity. Results: From January 2005 until December 2010 60 patients (median age 39 and median KPS 80) have been accrued and are now evaluable for response. Response rates on T2/FLAIR images were as follows: CR 0/60, PR 21/60 (35%), MR 14/60 (23%), SD 21/60 (35%) and PD 4/60 (7%). The clinical benefit was significant in 29/34 patients (85%). As for toxicity 5/60 (8%) patients stopped treatment for lymphopenia grade IV, whereas 11/31 patients (35%) were switched to the standard regimen of temozolomide. PET with methionine was added to MRI in 17 patients: in 10/17 (59%) a disappearance or a significant reduction of uptake was observed, being the reduction of seizures better correlated with the response on PET rather than that on MRI. 1p/19q codeletion was not associated with either the response or the clinical benefit, whereas the analysis of MGMT methylation and IDH1 mutations are ongoing. Thirty-nine (65%) patients are still free of tumor progression. Conclusions: Dose-dense TMZ seems to be active, especially in terms of clinical benefit, but the myelotoxicity could be a concern.

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The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽

10.1093/neuros/nyx265 ◽

2017 ◽

Vol 82 (6) ◽

pp. 808-814 ◽

Cited By ~ 20

Author(s):

Toral Patel ◽

Evan D Bander ◽

Rachael A Venn ◽

Tiffany Powell ◽

Gustav Young-Min Cederquist ◽

...

Keyword(s):

Cox Regression ◽

Extent Of Resection ◽

World Health ◽

Low Grade ◽

Wild Type ◽

Who Grade ◽

Cox Regression Analysis ◽

Low Grade Gliomas ◽

Grade Ii ◽

The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

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A Phase II Study of Dose-Dense Temozolomide and Lapatinib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma

Neuro-Oncology ◽

10.1093/neuonc/noaa240 ◽

2020 ◽

Author(s):

Mark R Gilbert ◽

Ying Yuan ◽

Jimin Wu ◽

Tito Mendoza ◽

Elizabeth Vera ◽

...

Keyword(s):

Spinal Cord ◽

Phase Ii ◽

Objective Response ◽

Symptom Burden ◽

Adult Patients ◽

Research Network ◽

Clinical Activity ◽

Low Grade ◽

Recurrent Ependymoma ◽

Dose Dense

Abstract Background No standard medical treatment exists for adult patients with recurrent ependymoma and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network (CERN) conducted a prospective phase II clinical trial of dose-dense temozolomide and lapatinib, targeting the unmethylated MGMT promoter status and increased expression of ErbB2 (HER2) and ErbB1 (EGFR) in ependymomas. Methods Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense temozolomide and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MDASI-BT/MDASI-SP were collected. Results The 50 patients enrolled had a median age of 43.5 years, median Karnofsky Performance Status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI 5.5,12.2); the 6-and 12-month PFS rates were 55% and 38%; with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients. Conclusions This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements is an option as a salvage regimen for adult patients with recurrent ependymoma.

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P04.09 Patterns of care and impact on survival of first salvage therapy in high-risk grade II gliomas following initial temozolomide

Neuro-Oncology ◽

10.1093/neuonc/noz126.104 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii30-iii30

Author(s):

A Pellerino ◽

L Bello ◽

M Conti Nibali ◽

F Bruno ◽

F Mo ◽

...

Keyword(s):

High Risk ◽

Salvage Therapy ◽

Molecular Data ◽

Low Grade ◽

Second Line ◽

Wild Type ◽

Second Line Chemotherapy ◽

Second Surgery ◽

Grade Ii ◽

Line Chemotherapy

Abstract BACKGROUND Initial chemotherapy with temozolomide (TMZ) may provide benefit in high-risk low-grade gliomas. To date, no standard treatment is validated at first progression. The aim of this retrospective study was to investigate the optimal salvage therapy after the first progression and the factors that influence the PFS and overall survival (OS). MATERIAL AND METHODS we evaluated 71 patients with an histological diagnosis of grade II glioma according to WHO 2016 classification, who were included in a phase II AINO (Italian Association for Neuro-Oncology) trial, and progressed following initial chemotherapy with TMZ. Molecular data were available in all patients: 32 (45.1%) patients were oligodendrogliomas IDH 1/2 mutated and 1p19q codeleted, 11 (15.5%) were diffuse astrocytomas IDH mutant, and 28 (39.4%) were diffuse astrocytomas IDH wild-type. Thirty-five (49.3%) patients were MGMT methylated. Median follow up was 144 months (range 23–180). RESULTS thirty-one patients (43.7%) underwent second surgery, 24 patients (33.8%) second-line chemotherapy (rechallenge with TMZ or nitrosoureas), and 16 patients (22.5%) radiotherapy with a median PFS of 58 months (IC 95% 49–116). The association between prognostic factors and type of salvage therapy revealed a prevalence of younger age (≤ 45 years), non-enhancing tumor and location in eloquent area among patients treated with second surgery or chemotherapy, while aolder age (> 45 years) and contrast-enhancing tumors prevailed among patients receiving radiotherapy. Overall, median PFS was 60 months after second surgery (IC95% 43–116) and chemotherapy (IC95% 51–69), and 38 months after radiotherapy (IC95% 15–64) (p 0.09). No significant benefit in length of PFS was achieved in oligodendrogliomas undergoing second surgery (60 months) as compared with oligodendrogliomas treated with radiation or chemotherapy (58 months, p 0.11). PFS of diffuse astrocytomas IDH wild-type following second surgery (53 months) did not differ from that of patients treated with adjuvant treatments (65 months, p 0.28). Overall, median OS from the first salvage therapy was 117 months (IC95% 93 - 123+): 120 months (IC95% 108–140+) after second surgery, 94 months (IC95% 75–117+) after chemotherapy, and 62 months (IC95% 27–112) after radiotherapy (p 0.04). Median OS (123 months, IC95% 106–154) was prolonged in oligodendrogliomas receiving second surgery as compared to those receiving radiotherapy or chemotherapy (93 months, IC 95% 61–112, p 0.07), while median OS in diffuse astrocytomas IDH wild-type did not differ between those who received second surgery or radiotherapy or chemotherapy. CONCLUSION: W hen feasible, reoperation as first salvage treatment following initial TMZ in grade II gliomas seems to offer a probability of a longer OS as compared with second-line chemotherapy or radiotherapy, and this could hold true especially for oligodendrogliomas.

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Temozolomide (TMZ) 1 week on/1 week off as initial treatment for progressive low grade oligodendroglial tumors: A phase II AINO study

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.2019 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 2019-2019 ◽

Cited By ~ 3

Author(s):

R. Soffietti ◽

R. Rudà ◽

E. Trevisan ◽

E. Laguzzi ◽

D. Guarneri ◽

...

Keyword(s):

Phase Ii ◽

Initial Treatment ◽

Low Grade ◽

Oligodendroglial Tumors

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RNA-Seq analysis of glioma tumors to reveal targetable gene fusions.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.2019 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 2019-2019 ◽

Cited By ~ 4

Author(s):

Deepa Suresh Subramaniam ◽

Joanne Xiu ◽

Shwetal Mehta ◽

Zoran Gatalica ◽

Jeffrey Swensen ◽

...

Keyword(s):

Life Sciences ◽

Gene Fusions ◽

Astrocytic Tumors ◽

Fusion Genes ◽

Rna Seq ◽

Wild Type ◽

Oligodendroglial Tumors ◽

Grade Ii ◽

Glioma Tumors ◽

Grade Iii

2019 Background: Fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. We aim to use RNA-sequencing to interrogate a large cohort of gliomas for targetable genetic fusions. Methods: Gliomas were profiled using the ArcherDx FusionPlex Assay at a CLIA-certified lab (Caris Life Sciences) and 52 gene targets were analyzed. Fusions with preserved kinase domains were investigated. Results: Among 404 gliomas tested, 39 (9.7%) presented potentially targetable fusions, of which 24/226 (11%) of glioblastoma (GBM), 5/42 (12%) of anaplastic astrocytoma (AA), 2/25 (8%) of grade II astrocytoma and 3 of 7 (43%) of pilocytic astrocytoma (PA) harbored targetable fusions. In GBMs, 1 of 15 (6.7%) IDH-mutated tumors had a fusion while 22 of 175 (12.6%) IDH-wild type tumors had fusions. 46 oligodendroglial tumors were profiled and no fusions were seen, which was lower than frequency of fusions in astrocytic tumors (34/300, p = 0.0236). The most frequent fusions seen involved FGFR3 (N = 12), including 10 FGFR3-TACC3 (1 AA, 6 GBM and 3 glioma NOS); 1 FGFR3-NBR1 (AA) and 1 FGFR3-BRAP (GBM). 11 fusions involving MET were seen, 10 in GBM and 1 in AA. The most common MET fusion was PTPRZ1-MET (1 in AA and 4 in GBM), followed by ST7-MET (N = 3, GBM), CAPZA2-Met (N = 2, GBM) and TPR-MET (N = 1, GBM). 8 NTRK fusions were seen; 1 involving NTRK1 (BCAN-NTRK1, PA), 6 NTRK2 (1 NOS1AP-NTRK2 in AA; GKAP1-NTRK2, KCTD8-NTRK2, TBC1D2-NTRK2 and SOSTM1-NTRK2, 1 each in GBM and 1 VCAN-NTRK2 in grade II astrocytoma) and 1 NTRK3 (EML4-NTRK3 in GBM). EGFR fusions (2 EGFR-SEPT14 and 1 EGFR-VWC2) were seen in 3 GBMs, BRAF in 3 (1 KIAA1549-BRAF, 1 LOC100093631-BRAF in PA and 1 ZSCAN23-BRAF in glioma NOS) and PDGFRA (RAB3IP-PDGFRA, in GBM) in 1. C11orf95-RELA fusions were seen in 2 of 3 grade III ependymomas but not in the 2 grade II ependymomas. Conclusions: We report targetable fusion genes involving NTRK, MET, EGFR, FGFR3, BRAF and PDGFRA including novel fusions that haven’t been previously described in gliomas (e.g., EGFR-VWC2; FGFR3-NBR1). Fusions were seen in over 10% of astrocytic tumors, while none was seen oligodendrogliomas. Identification of such kinase-associated fusion transcripts may allow us to exploit therapeutic opportunities with targeted therapies in gliomas.

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Contrast-enhanced ultrasonography (CEUS) in retroperitoneal liposarcomas

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.20514 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 20514-20514

Author(s):

M. Brandi ◽

G. Badalamenti ◽

F. Sorrentino ◽

L. Vizzini ◽

L. Incorvaia ◽

...

Keyword(s):

Ct Scan ◽

Contrast Enhancement ◽

Tumor Response ◽

Average Diameter ◽

Clear Correlation ◽

Low Grade ◽

Mechanical Index ◽

Malignancy Grade ◽

Number Of Patients ◽

Response To Chemotherapy

20514 Background: CEUS with second-generation contrast agents has been proposed to monitor tumor response to imatinib in patients with metastatic GIST. There are no data in patients with other sarcomas. Our aim was to assess the value of CEUS as a marker of tumor response in retroperitoneal liposarcoma, in addition to its ability to render the baseline malignancy grade of the disease. Methods: CEUS was performed after a SonoVue injection (Bracco, Milano, Italia). SonoVue is a suspension of microbubbles of exafluoride sulphure gas (average diameter 3 μm) with a phospholipidic shell. A low mechanical index (MI<0.09) was used in order to minimize microbubbles rupture. Ultrasound device systems (Philips ATL HDI 5000, Bothel, Washington) with a broandband probe (2–5 Mhz) and specific contrast agent algorithms (Pulse Inversion Harmonic Imaging) were used. The use of this algorithm allowed a real time imaging of all vascular phases (arterial, portal and late). All patients underwent CT scan, PET tomography and routine blood examinations. Ten patients with retroperitoneal liposarcomas were enrolled in this study (5 high grade, 3 intermediate grade, 2 low grade). Results: Five males and five females with metastatic or relapsed disease were enrolled. Median age was 57 years (range 40–70). All underwent chemotherapy with Ifosfamide and Doxorubicin. In all patients there was a clear correlation between contrast enhancement and grading: in low-grade patients there was no contrast enhancement, while the highest level of enhancement was seen in undifferentiated sarcomas. With regard to tumor response to chemotherapy, only 4 patients were evaluable. One patient had a PR and 3 patients had PD. In the 3 patients with PD CEUS showed contrast enhancement, PET was uptaking, but CT scan did not detect any change. In the patient with a PR, strong decrease of tumor perfusion on CEUS and uptaking on PET was seen, again with no change on CT scan. Conclusions: These preliminary observations suggest that CEUS may be more useful than CT scan on assessing tumor response in retroperitoneal sarcomas, and may predict the baseline malignancy grade. Data on a larger number of patients will be presented. No significant financial relationships to disclose.

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Wnt pathway markers in low-grade and high-grade gliomas

Ideggyógyászati Szemle ◽

10.18071/isz.74.0349 ◽

2021 ◽

Vol 74 (9-10) ◽

pp. 349-355

Author(s):

Ádám Nagy ◽

Márton Tompa ◽

Zoltán Krabóth ◽

Ferenc Garzuly ◽

Alexandra Maráczi ◽

...

Keyword(s):

Wnt Pathway ◽

Low Grade ◽

Normal Brain ◽

Beta Catenin ◽

Oligodendroglial Tumors ◽

Molecular Approaches ◽

Idh1 R132h ◽

Mutational Status ◽

In The Wild ◽

Grade Ii

Aberrant activation of the Wnt pathway contributes to differentiation and maintenance of cancer stem cells underlying gliomagenesis. The aim of our research was to determine as to what degrees some Wnt markers are expressed in gliomas of different grades, lineages and molecular subtypes. Nine grade II, 10 grade III and 72 grade IV surgically removed, formalin-fixed paraffin-embedded glioma specimens were included. Mutation status of IDH1 codon 132 was defined by immunohistochemistry and pyrosequencing in all tumors. Grade II and III astrocytic and oligodendroglial tumors were further tested for the expression of p53 and ATRX by immunohistochemistry, and codeletion of 1p19q by fluorescent in situ hybridization. Expression levels of the non-canonical Wnt5a and Fzd2, and the canonical Wnt3a and beta-catenin Wnt pathway markers were determined by immunohistochemistry, and compared between subgroups stratified according to grade, lineage and the presence or absence of IDH1 R132H/C mutations. In the normal brain – grade II-IV glioma comparisons, a gradual increase was observed for the expressions of Wnt5a, Wnt3a, Fzd2 and beta-catenin. In the astroglial and oligodendroglial lineages of grade II and III gliomas, only the Wnt5a expression was significantly higher in the astroglial subgroup. Stratification according to the IDH1 status resulted in a significant increase of the Wnt3 expression in the wild type grade II-IV gliomas. These data extend previous observations and show a correlation of Wnt pathway activity with glioma grade. Further investigations of the Wnt marker expression regulation according to glioma lineage or IDH gene mutational status are in progress by using more exact molecular approaches.

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