Updating the grading criteria for adult diffuse gliomas: beyond the WHO2016CNS classification

Komori, Takashi

doi:10.1007/s10014-020-00358-y

Cited by 28 publications

(12 citation statements)

References 15 publications

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“…The use of different thresholds for grading assessment margin could explain the inconsistent results obtained in different studies on prognosis and molecular profile of IDHwt grade II and III gliomas and, in our view, represents an urgent issue to address in the forthcoming WHO classification. 23 The grading criteria used here have been widely used in the past and have been adopted by the cIMPACT to separate grade II and III IDHmut diffuse astrocytomas 14 : in the same way, they allow here a prognostic stratification of IDHwt gliomas, suggesting that the same mitotic threshold is associated with different outcome in both IDHmut and IDHwt gliomas.…”

Section: Neuro-oncologymentioning

confidence: 99%

IDH-wildtype lower-grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification

et al. 2020

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Background IDH-wildtype (IDHwt) grade II gliomas are a rare and heterogeneous entity. Survival and prognostic factors are poorly defined. Methods We searched retrospectively all patients diagnosed with diffuse WHO grade II and III gliomas at our center (1989-2020). Results Out of 517 grade II gliomas, 47 were “diffuse astrocytomas, IDHwt”. Tumors frequently had fronto-temporo-insular location (28/47, 60%) and infiltrative behavior. We found TERT promoter mutations (23/45, 51%), whole chromosome 7 gains (10/37, 27%), whole chromosome 10 losses (10/41, 24%), and EGFR amplifications (4/43, 9%) but no TP53 mutations (0/22, 0%). Median overall survival (OS) was 59 months (vs. 19 months for IDHwt grade III gliomas (p< 0.0001). Twenty-nine patients (29/43, 67%) met the definition of molecular glioblastoma according to cIMPACT-NOW update3. Median OS in this subset was 42 months, which was shorter compared to patients with IDHwt grade II gliomas not meeting this definition (median OS: 57 months), but substantially longer compared to IDHwt grade III gliomas meeting the definition for molecular glioblastoma (median OS: 17 months, p<0.0001). Most patients with IDHwt grade II gliomas met cIMPACT criteria because of isolated TERT promoter mutations (16/26, 62%), which were not predictive of poor outcome (median OS: 88 months). Actionable targets, including 5 gene fusions involving FGFR3, were found in 7 patients (24%). Conclusions Our findings highlight the importance of histological grading and molecular profiling for the prognostic stratification of IDHwt gliomas and suggest some caution when assimilating IDHwt grade II gliomas to molecular glioblastomas, especially those with isolated TERT promoter mutation.

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Section: Neuro-oncologymentioning

confidence: 99%

IDH-wildtype lower-grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification

et al. 2020

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“…[3][4][5] Case 2 was diagnosed with diffuse astrocytoma, with molecular features of glioblastoma, WHO grade IV. 2,6,7 Although both cases revealed similar pathologies, the clinical outcomes were completely distinct. Thus, radiological images, including CT and MRI, with a perfusion study of both cases were compared to improve diagnostic accuracy.…”

Section: Discussionmentioning

confidence: 91%

“…The patient in case 1 was believed to have tumefactive demyelinating disease (TDL), [3][4][5] whereas in the patient in case 2, we detected a TERT promoter mutation which indicated diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma, WHO grade IV. 2,6,7 For both cases, radiological and pathological comparisons were conducted.…”

Section: Introductionmentioning

confidence: 99%

Radiologic–pathologic association of tumor‐like lesions with inflammation in cerebral white matter: Comparison of two cases with distinct clinical outcomes

et al. 2021

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Here, we report two cases showing tumor-like white matter lesions; one case was diagnosed as having inflammatory disease, and the other was diagnosed as having astrocytoma. Their outcomes were completely distinct despite similar pathology. Prior to biopsy, perfusion computed tomography (CT) and magnetic resonance imaging (MRI) were conducted. The two mass-forming lesions were distinct in edema level and vascularity patterns on CT and MRI. However, pathological examination of brain biopsy specimens revealed commonalities, including (1) proliferation of glial cells, (2) perivascular lymphocytic infiltration, and (3) appearance of numerous macrophages. Although atypical astrocytes proliferated in both cases, nuclear atypia was more distinct in case 2 than in case 1. The immunohistochemical results were the same for both cases: isocitrate dehydrogenase 1 (IDH1) R132H mutation was negative, and alpha thalassaemia mental retardation X-linked (ATRX) was retained. Faint immunoreactivity for p53 was observed in a few glial cells, and Ki-67 immunoreactive cells were markedly reduced in numbers (< 1%). Inflammatory reactions were evident in both cases: T cells dominantly infiltrated over B cells in the perivascular area in case 1, whereas both T and B cells infiltrated in case 2. Molecular analysis revealed wild-type IDH1 and IDH2 in both cases. However, a telomerase reverse transcriptase (TERT) sequence mutation was detected in case 2 but not in case 1.Eventually, case 1 was diagnosed as having inflammatory lesions, whereas case 2 was diagnosed as having diffuse astrocytoma associated with inflammatory reactions. The prognosis was favorable for case 1, whereas case 2 died 10 months following biopsy. These data indicated the diagnostic value of molecular analysis, for example, a TERT mutation, in association with the radiological findings. Although in case 2, histopathological evidence did not suggest high-grade glioma, the case met the new diagnostic criteria: "diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma, World Health Organization (WHO) grade IV," according to cIMPACT-NOW, update 3. Thus, interdisciplinary approaches are essential for accurate diagnosis of newly categorized white matter diseases.

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“…Currently, most NOTCH inhibitors remain in clinical phase I and II trials, but several NOTCH inhibitors had only a modest efficacy in the initial stage, with an unsatisfactory outcome (48,49). Since the tumor microenvironment contains a complex mixture of biochemical and biophysical cues that modulate cell behavior (33,50), possible reasons for these unsatisfied results may have been the heterogeneity of glioma and the crosstalk between the NOTCH pathway and other molecules.…”

Section: Discussionmentioning

confidence: 99%

GASC1 promotes glioma progression by enhancing NOTCH1 signaling

et al. 2021

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Recent studies have reported that gene amplified in squamous cell carcinoma 1 (GASC1) is involved in the progression of several types of cancer. However, whether GASC1 promotes glioma progression remains unknown. Therefore, the present study aimed to investigate the effect of GASC1 exposure on glioma tumorigenesis. The western blot demonstrated that grade III and IV glioma tissues exhibited a higher mRNA and protein expression of GASC1. Moreover, CD133 + U87 or U251 cells from magnetic cell separation exhibited a higher GASC1 expression. Invasion Transwell assay, clonogenic assay and wound healing assay have shown that GASC1 inhibition using a pharmacological inhibitor and specific short hairpin (sh)RNA suppressed the invasive, migratory and tumorsphere forming abilities of primary culture human glioma cells. Furthermore, GASC1-knockdown decreased notch receptor (Notch) responsive protein hes family bHLH transcription factor 1 (Hes1) signaling. GASC1 inhibition reduced notch receptor 1 (NOTCH1) expression, and a NOTCH1 inhibitor enhanced the effects of GASC1 inhibition on the CD133 + U87 or U251 cell tumorsphere forming ability, while NOTCH1 overexpression abrogated these effects. In addition, the GASC1 inhibitor caffeic acid and/or the NOTCH1 inhibitor DAPT (a γ-Secretase Inhibitor), efficiently suppressed the human glioma xenograft tumors. Thus, the present results demonstrated the importance of GASC1 in the progression of glioma and identified that GASC1 promotes glioma progression, at least in part, by enhancing NOTCH signaling, suggesting that GASC1/NOTCH1 signaling may be a potential therapeutic target for glioma treatment.

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Updating the grading criteria for adult diffuse gliomas: beyond the WHO2016CNS classification

Cited by 28 publications

References 15 publications

IDH-wildtype lower-grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification

IDH-wildtype lower-grade diffuse gliomas: the importance of histological grade and molecular assessment for prognostic stratification

Radiologic–pathologic association of tumor‐like lesions with inflammation in cerebral white matter: Comparison of two cases with distinct clinical outcomes

GASC1 promotes glioma progression by enhancing NOTCH1 signaling

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