Immunohistochemical expression of glial fibrillary acidic protein and CAM5.2 in glial tumors and their role in differentiating glial tumors from metastatic tumors of central nervous system

Goyal, Rama; Mathur, SK; Gupta, Sumiti; Goyal, Rahul; Kumar, Sanjay; Batra, Akshay; Hasija, Sonia; Sen, Rajeev

doi:10.4103/0976-3147.168426

Cited by 22 publications

(19 citation statements)

References 13 publications

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“…Terada, 2015 Low grade (n = 40) , grade IV (n = 16) GFAP reactivity in all tumors. Goyal et al, 2015 Grade II ((n = 43), grade III and IV (n = 33)…”

Section: Inconsistent Correlation Of Gfap Expression Levels To Astrmentioning

confidence: 99%

Importance of GFAP isoform‐specific analyses in astrocytoma

Bodegraven

Asperen

Robe

et al. 2019

Glia

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Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and treatment strategies. Although recent developments in the molecular biology of glioma have improved diagnosis, classical histological methods and biomarkers are still being used. The glial fibrillary acidic protein (GFAP) is a classical marker of astrocytoma, both in clinical and experimental settings. GFAP is used to determine glial differentiation, which is associated with a less malignant tumor. However, since GFAP is not only expressed by mature astrocytes but also by radial glia during development and neural stem cells in the adult brain, we hypothesized that GFAP expression in astrocytoma might not be a direct indication of glial differentiation and a less malignant phenotype. Therefore, we here review all existing literature from 1972 up to 2018 on GFAP expression in astrocytoma patient material to revisit GFAP as a marker of lower grade, more differentiated astrocytoma. We conclude that GFAP is heterogeneously expressed in astrocytoma, which most likely masks a consistent correlation of GFAP expression to astrocytoma malignancy grade. The GFAP positive cell population contains cells with differences in morphology, function, and differentiation state showing that GFAP is not merely a marker of less malignant and more differentiated astrocytoma. We suggest that discriminating between the GFAP isoforms GFAPδ and GFAPα will improve the accuracy of assessing the differentiation state of astrocytoma in clinical and experimental settings and will benefit glioma classification.

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“…Terada, 2015 Low grade (n = 40) , grade IV (n = 16) GFAP reactivity in all tumors. Goyal et al, 2015 Grade II ((n = 43), grade III and IV (n = 33)…”

Section: Inconsistent Correlation Of Gfap Expression Levels To Astrmentioning

confidence: 99%

Importance of GFAP isoform‐specific analyses in astrocytoma

Bodegraven

Asperen

Robe

et al. 2019

Glia

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“…In addition, CD31/PSA co-staining showed more VM channels in HGG than LGG (3.224 ± 0.3600 vs. 1.108 ± 0.2577, p < 0.001), suggesting that the VM-forming ability was remarkably enhanced in HGG compared with LGG. The abundant expression of GFAP in the cells surrounding the VM channels confirmed the cells as glial tumor cells[24,25]. Immunofluorescence staining showed CD31-/CAV1+ staining can differentiate VM-like structures from true blood vessels, and CAV1 may play a role in VM-like structures formedFigure 2A.…”

mentioning

confidence: 79%

Caveolin-1 promotes tumor cell proliferation and vasculogenic mimicry formation in human glioma

Chen

Cheng

Wang

et al. 2019

Preprint

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Background: Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. Methods: In this study, we examined CAV-1 expression levels and vasculogenic mimicry in human glioma cell lines and in 94 human gliomas with different grades and presented cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, Western blotting, CCK-8 assays, tubule formation assays. Results: Cav-1 expression and VM formation were positively correlated with each other and both are closely associated with glioma development and progression as evidenced by the presence of cystic tumor, the shortened survival time and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Conclusion: Collectively, our study identifies Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.

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“…GFAP is the most frequently used marker in diagnostic neuro-oncology. Positive reaction to GFAP has been demonstrated in astrocytoma and astrocytic cells of mixed gliomas [22]. However, previous researchers selected only potential biomarkers for their studies to identify their role in brain tumor pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Immunohistochemical Biomarkers in Patients with Astrocytic Brain Tumor

Ochirjav,

Dorj,

Baldandorj

et al. 2018

Cent. Asian j. Med. Sci.

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Objectives: Astrocytoma is a common primary malignant brain tumor and it is typically associated with poor outcome. In this study, we aimed to determine role of various immunohistochemical (IHC) biomarkers and their relationship with patient prognosis. Methods: Patients who underwent surgery for astrocytic brain tumor were selected. Tissue specimens were collected from surgically removed tumors and stained by various IHC stains. All-cause mortality was chosen for study endpoint. Results: A total of 133 patients with who underwent surgery for astrocytic brain tumor were included (mean age 38±19 and 49.6% male). During follow-up, 84 patients (63%) died and the median time of death was 8 months (IQR 4; 16) after hospital discharge. Patients who died had higher tumor grade (60.7% vs. 34.7%, p<0.01). After adjustment of possible predictors, surgical type (HR=0.51, 95% CI 0.31-0.82, p<0.01), expression level of Ki67 (HR=1.02, 95% CI 1.00-1.04, p<0.05) and p53 (HR=1.01, 95% CI 1.00-1.02, p<0.05) were independently associated with long term mortality. Kaplan-Meier estimation showed overexpression of WT1 (42% vs. 52%, p<0.05) and Ki67 (27% vs. 58%, p<0.001) are associated with poor survival. Conclusion: IHC biomarkers are independently associated with long term prognosis in patients with astrocytic brain tumor. Overexpression of WT1 and Ki67 marker are associated with poor survival.

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Immunohistochemical expression of glial fibrillary acidic protein and CAM5.2 in glial tumors and their role in differentiating glial tumors from metastatic tumors of central nervous system

Cited by 22 publications

References 13 publications

Importance of GFAP isoform‐specific analyses in astrocytoma

Importance of GFAP isoform‐specific analyses in astrocytoma

Caveolin-1 promotes tumor cell proliferation and vasculogenic mimicry formation in human glioma

Prognostic Value of Immunohistochemical Biomarkers in Patients with Astrocytic Brain Tumor

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