GATA3 positivity is associated with poor prognosis in patients with oesophageal squamous cell carcinoma

Chi, Zhikai; Balani, Jyoti; Gopal, Purva; Hammer, Suntrea T.G.; Xu, Jing; Peng, Lan

doi:10.1136/jclinpath-2021-208035

Cited by 5 publications

(6 citation statements)

References 34 publications

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“…These transcription factors act as tumor suppressors in some cancers [72][73][74][75]. However, consistent with results of the present study, their activities promote aggressive behavior in other cancers, including those of mesenchymal origin [76][77][78][79]. Our results are therefore consistent with those reported in many previous studies, most of which have been conducted on human tumors, and underscore commonalities in mechanisms responsible for tumorigenesis and cancer behavior in both species.…”

Section: Discussionsupporting

confidence: 93%

Comparative whole transcriptome analysis of gene expression in three canine soft tissue sarcoma types

et al. 2022

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Soft tissue sarcomas are pleiotropic tumors of mesenchymal cell origin. These tumors are rare in humans but common in veterinary practice, where they comprise up to 15% of canine skin and subcutaneous cancers. Because they present similar morphologies, primary sites, and growth characteristics, they are treated similarly, generally by surgical resection followed by radiation therapy. Previous studies have examined a variety of genetic changes as potential drivers of tumorigenesis and progression in soft tissue sarcomas as well as their use as markers for soft tissue sarcoma subtypes. However, few studies employing next generation sequencing approaches have been published. Here, we have examined gene expression patterns in canine soft tissue sarcomas using RNA-seq analysis of samples obtained from archived formalin-fixed and paraffin-embedded tumors. We provide a computational framework for using resulting data to categorize tumors, perform cross species comparisons and identify genetic changes associated with tumorigenesis. Functional overrepresentation analysis of differentially expressed genes further implicate both common and tumor-type specific transcription factors as potential mediators of tumorigenesis and aggression. Implications for tumor-type specific therapies are discussed. Our results illustrate the potential utility of this approach for the discovery of new therapeutic approaches to the management of canine soft tissue sarcomas and support the view that both common and tumor-type specific mechanisms drive the development of these tumors.

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Section: Discussionsupporting

confidence: 93%

Comparative whole transcriptome analysis of gene expression in three canine soft tissue sarcoma types

et al. 2022

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“…In another study, Chi et al [21] detected GATA3 immunopositivity in 28% of the esophageal SCC cases studied; the survival rate was lower in these cases compared to patients who did not exhibit immunoreactivity. The authors concluded that GATA3 positivity was associated with a poor prognosis.…”

Section: Discussionmentioning

confidence: 87%

Relationship between tumor thickness and GATA3 immunoexpression in lip and tongue squamous cell carcinomas

Vital

Carvalho

Maia

et al. 2023

Preprint

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Objectives Our aim was to evaluate tumor thickness in cases of oral squamous cell carcinoma (SCC) and to correlate it with histological grade of malignancy and GATA3 immunoreactivity. Materials and Methods Sixty specimens (30 lower lip SCCs [LLSCCs] and 30 oral tongue SCCs [OTSCCs]) were scanned and digitized for the subsequent measurement of tumor thickness, histopathological examination, and quantitative analysis of GATA3 in the parenchyma and stroma of the tumors. Results Tumor thickness was lower in LLSCC cases compared to OTSCCs (p: 0.000). Immunohistochemical analysis of GATA3 in parenchyma, stroma and both compartments showed higher immunoreactivity in LLSCCs compared to OTSCCs (p: 0.000). We observed a negative correlation between tumor thickness and GATA3 expression in parenchyma (p: 0.014), stroma (p: 0.032), and both compartments (parenchyma and stroma) (p: 0.012). Conclusions Our results revealed the presence of GATA3 in all cases both in the parenchyma and in the stroma. Higher expression was more related to LLSCCs, which are known to be less aggressive tumors than OTSCCs. A greater tumor thickness was found in OTSCCs, which was correlated with lower expression of GATA3, suggesting that this protein is involved in the inhibition of proliferative, migratory, and invasive capacity. Clinical relevance: These findings can provide a basis for the identification of new therapeutic targets for OSCC, reinforcing the use of GATA3 as a biomarker in the neoplasms studied.

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“…36 The expression of GATA3 in SCCs appears to vary by anatomic site and by analysis, with cutaneous SCCs reportedly being variably positive, 10 and noncutaneous SCCs, including cervical, laryngeal, and pulmonary SCCs displaying much less frequent GATA3 expression. 1,10,[35][36][37] A prognostic role may be emerging for GATA3 expression in SCCs at some sites: Chi et al 9 recently reported that GATA3 expression is associated with poor prognosis in esophageal SCC. Furthermore, GATA3 appears to be mechanistically involved in squamous cell carcinogenesis and/or progression at various sites.…”

Section: Discussionmentioning

confidence: 99%

“…7 Conversely, the expression of GATA3 has been associated with worse prognosis in soft tissue tumors, 8 and esophageal squamous cell carcinoma (SCC). 9 Among the skin and associated cutaneous structures, the epidermis, sebaceous glands, hair shafts, eccrine, and apocrine sweat glands express GATA3 protein, and many neoplasms, particularly basal cell carcinoma and SCC can be immunoreactive for GATA3, 1,10 although the reported frequencies of expression have varied significantly. Not much is known about GATA3 expression patterns in vulvar squamous cell carcinoma (VSCC).…”

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confidence: 99%

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GATA3 Expression in HPV-associated and HPV-independent Vulvar Squamous Cell Carcinomas: Patterns of Expression and Prognostic Significance

Vaziri Fard,

Zare,

Fadare

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Substantial diminution or loss of GATA3 expression is reportedly frequent in human papillomavirus–independent (HPVI), p53-mediated vulvar intraepithelial neoplasia. Herein, we study GATA3 expression in vulvar squamous cell carcinoma (VSCC) and assess its clinicopathologic significance. Eighty-six cases of VSCC diagnosed at a single institution were immunohistochemically assessed for their expression of GATA3, as well as any possible relationships with patient outcomes and other clinicopathologic parameters. Given that GATA3 expression pattern in the normal vulvar epidermis is typically strong basal staining with a uniform upward extension until at least the mid epidermal layers, VSCCs were scored using a previously reported tripattern system: pattern 0 (>75% tumor staining), pattern 1 (25% to 75% staining), and pattern 2 (<25% staining). Severe loss of GATA3 expression (pattern 2) was present in both human papillomavirus–associated (HPVA) and HPVI VSCC but was significantly more common in HPVI cases (P<0.001). Among 52 HPVA VSCCs, 16 (30.7%), 15 (28.8%), and 21 (40.3%) cases showed patterns 0, 1, 2 staining whereas among 34 HPVI VSCCs, the respective frequencies were 1 (2.9%), 5 (14.7%), and 28 (82.3%). None of the 30 p53 abnormal VSCCs showed pattern 0 staining (0%). Five (16.6%) and 25 (83.3%) showed patterns 1 and 2 staining, respectively. On univariate analysis, the pattern 2 cohort showed a significantly worse overall survival (OS) and disease-free survival (DFS) than the pattern 0 or 1 cohort (P=0.011 and 0.024, respectively), but this finding was not independent of stage on multivariate analysis (P=0.34; hazard ratio: 1.82; 95% CI: 0.55-6.06). Subgroup analysis of the p53 wild-type cases showed significantly worse OS for pattern 2 than the pattern 0 or 1 cohorts, independent of stage (P=0.04; hazard ratio: 6.5; 95% CI: 1.08-39.8). Subgroup analysis of p53 abnormal cases, however, showed no difference in OS and DFS among the 3-tiered GATA3 cohorts. In summary, loss of GATA3 may be seen in both HPVA and HPVI VSCCs but is significantly more common in HPVI SCCs. Loss or substantial diminution of GATA3 expression (pattern 2) is a negative prognostic factor in vulvar SCCs, but only in the p53 wild-type subset, where its negative prognostic significance appears to be independent of stage.

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GATA3 positivity is associated with poor prognosis in patients with oesophageal squamous cell carcinoma

Cited by 5 publications

References 34 publications

Comparative whole transcriptome analysis of gene expression in three canine soft tissue sarcoma types

Comparative whole transcriptome analysis of gene expression in three canine soft tissue sarcoma types

Relationship between tumor thickness and GATA3 immunoexpression in lip and tongue squamous cell carcinomas

GATA3 Expression in HPV-associated and HPV-independent Vulvar Squamous Cell Carcinomas: Patterns of Expression and Prognostic Significance

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