GATA3 is a reliable marker for neuroblastoma in limited samples, including FNA Cell Blocks, core biopsies, and touch imprints

Wiles, Austin; Karrs, Jeremiah; Pitt, Susan C.; Almenara, Jorge A.; Powers, Celeste N.; Smith, Steven C.

doi:10.1002/cncy.21927

Cited by 18 publications

(21 citation statements)

References 29 publications

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“…However, it may be noted that neuronal differentiation is reported in familial Wilms tumour and caution must be exercised in such cases. Recently, GATA‐3 was identified as a novel NB marker which would be useful in such problematic cases . NB also showed consistent negativity for other markers such as vimentin, CD99, desmin, myogenin and CD45 used for distinction from other small blue round cell tumours.…”

Section: Discussionmentioning

confidence: 91%

Cytopathological spectrum of peripheral neuroblastic tumours in fine needle aspiration cytology and categorisation as per International Neuroblastoma Pathology Classification

et al. 2019

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Objective The aim of this analysis was to describe the cytopathology spectrum of peripheral neuroblastic tumours (NTs) including neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN). Feasibility of applying the International Neuroblastoma Pathology Classification (INPC) to further subtype NTs in cytology was evaluated. Methods All peripheral NTs reported on fine needle aspiration during 2011‐2015 were retrieved and detailed cytomorphological evaluation was performed. Based on INPC criteria, NBs were further categorised as undifferentiated, poorly differentiated and differentiating subtypes. Mitotic‐karyorrhectic index was evaluated. Immunocytochemistry on cell blocks was reviewed wherever available. MYCN amplification by fluorescence in situ hybridisation was performed in 11 cases on smears. Results A total of 90 cases including 83 NBs, six GNB and one GN were evaluated. The age range was 12 days‐12 years, with 55 males and 45 females. Both the primary and metastatic locations were aspirated. Applying the INPC criteria, there were 61 poorly differentiated, 14 undifferentiated, eight differentiating NB and six GNB. Immunocytochemistry on cell blocks showed positivity for at least two neuronal markers in NB. Mitotic‐karyorrhectic index was high in 63, low in 22 and intermediate in two cases, respectively. MYCN amplification by fluorescence in situ hybridisation was feasible on smears and was amplified in 6 out of 11 cases tested. Conclusion Peripheral NT types including NB, GNB and GN have distinctive cytomorphology. NBs can be further subtyped as undifferentiated, poorly differentiated and differentiating subtypes as per INPC criteria.

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Section: Discussionmentioning

confidence: 91%

Cytopathological spectrum of peripheral neuroblastic tumours in fine needle aspiration cytology and categorisation as per International Neuroblastoma Pathology Classification

et al. 2019

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“…The cellular composition of neuroblastomas does not appear to correspond to clinical outcome directly, although epigenetic plasticity may allow interconversion between the cell types, driving drug resistance 55,56 . Others have previously shown a high level of GATA3 expression in neuroblastoma 50,57 , and suggested that GATA3 is a useful distinguishing diagnostic marker for neuroblastoma 58 . Our results showed that a complete absence of GATA3 DNA methylation (Fig.…”

Section: Discussionmentioning

confidence: 97%

Epigenetic deregulation of GATA3 in neuroblastoma is associated with increased GATA3 protein expression and with poor outcomes

Almutairi

Charlet

Dallosso

et al. 2019

Sci Rep

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To discover epigenetic changes that may underly neuroblastoma pathogenesis, we identified differentially methylated genes in neuroblastoma cells compared to neural crest cells, the presumptive precursors cells for neuroblastoma, by using genome-wide DNA methylation analysis. We previously described genes that were hypermethylated in neuroblastoma; in this paper we report on 67 hypomethylated genes, which were filtered to select genes that showed transcriptional over-expression and an association with poor prognosis in neuroblastoma, highlighting GATA3 for detailed studies. Specific methylation assays confirmed the hypomethylation of GATA3 in neuroblastoma, which correlated with high expression at both the RNA and protein level. Demethylation with azacytidine in cultured sympathetic ganglia cells led to increased GATA3 expression, suggesting a mechanistic link between GATA3 expression and DNA methylation. Neuroblastomas that had completely absent GATA3 methylation and/or very high levels of protein expression, were associated with poor prognosis. Knock-down of GATA3 in neuroblastoma cells lines inhibited cell proliferation and increased apoptosis but had no effect on cellular differentiation. These results identify GATA3 as an epigenetically regulated component of the neuroblastoma transcriptional control network, that is essential for neuroblastoma proliferation. This suggests that the GATA3 transcriptional network is a promising target for novel neuroblastoma therapies.

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“…17 The rs3824662 single nucleotide polymorphism (SNP) is located within intron 3 of the GATA3 gene and encodes the GATA-binding protein 3 isoform 2. 18 GATA3 is considered to be a reliable diagnostic marker for neuroblastoma 19 and renal cell carcinomas 20 and its expression is associated with breast carcinomas. 21 Na et al 22 performed a three-stage GWAS for GATA3 genetic variant and benign prostatic hyperplasia (BPH) of men from three independent populations.…”

Section: Resultsmentioning

confidence: 99%

“…GATA3 is considered to be a reliable diagnostic marker for neuroblastoma 19 and renal cell carcinomas 20 and its expression is associated with breast carcinomas. 21 Na et al.…”

Section: Discussionmentioning

confidence: 99%

GATA3 rs3824662 gene polymorphism as possible risk factor for systemic lupus erythematosus

Mosaad

Hammad

Elghzaly

et al. 2018

Lupus

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Background There is no report about the association between GATA3 rs3824662 polymorphism and systemic lupus erythematosus (SLE). Objective To investigate the possible role of GATA3 rs3824662 polymorphism as a susceptibility risk factor for either adult SLE (aSLE) or pediatric SLE (pSLE) and to evaluate its role in the development of lupus nephritis (LN) in pSLE. Methods Typing of GATA3 rs3824662 polymorphism was done using real-time polymerase chain reaction for three groups; 104 pSLE patients, 140 aSLE patients and 436 age- and sex-matched healthy controls. Results Non-significant differences were found between SLE patients and healthy controls for the allele and genotype frequencies of GATA3 rs3824662 ( p > 0.05). In pSLE; the AC genotype was associated with LN ( p = 0.04); the A allele and AC genotype were associated with persistent proteinuria ( p = 0.036 and 0.01, respectively) and both the A allele and AA genotype were associated with higher chronicity index ( p = 0.031 and 0.04, respectively). In aSLE; the C allele was associated with cellular cast ( p = 0.03) and thrombocytopenia ( p = 0.01). Logistic regression analysis revealed significant association between the AC+AA genotypes and the prediction of LN and renal active disease in pSLE ( p = 0.04 and 0.01, respectively). Conclusion GATA3 rs3824662 is not associated with susceptibility to SLE either in adult or in pediatric patients; however, in pSLE patients, the heterozygous AC genotype could be considered a risk factor for LN. At the same time, the AC and AA genotypes could be considered as predictors for LN and active renal disease. However, the small sample size is a limiting factor of the present study when interpreting the positive association.

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GATA3 is a reliable marker for neuroblastoma in limited samples, including FNA Cell Blocks, core biopsies, and touch imprints

Abstract: GATA3 is a reliable diagnostic marker for NBs not only in scant/limited surgical specimens but also in cytologic samples, including air-dried touch imprints, which have previously been undescribed for this marker. Cancer Cytopathol 2017;125:940-6. © 2017 American Cancer Society.

Cited by 18 publications

References 29 publications

Cytopathological spectrum of peripheral neuroblastic tumours in fine needle aspiration cytology and categorisation as per International Neuroblastoma Pathology Classification

Cytopathological spectrum of peripheral neuroblastic tumours in fine needle aspiration cytology and categorisation as per International Neuroblastoma Pathology Classification

Epigenetic deregulation of GATA3 in neuroblastoma is associated with increased GATA3 protein expression and with poor outcomes

GATA3 rs3824662 gene polymorphism as possible risk factor for systemic lupus erythematosus

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