Prognostic stratification of muscle invasive urothelial carcinomas using limited immunohistochemical panel of Gata3 and cytokeratins 5/6, 14 and 20

Jangir, Hemlata; Nambirajan, Aruna; Seth, Amlesh; Sahoo, Ranjit Kumar; Dinda, Amit Kumar; Nayak, Brusabhanu; Kaushal, Seema

doi:10.1016/j.anndiagpath.2019.08.001

Cited by 31 publications

(34 citation statements)

References 39 publications

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“…In the current meta-analysis data was insufficient to determine the prognostic value of ERb due to differences in the methodology and data reported among individual studies. Regarding GATA3, pooled analysis indicated that positive expression was significantly associated with lower risk of recurrence, which is in agreement with the results of the individual studies included in this analysis (112,113) and others that didn't meet including criteria (73). This result independently confirms the prognostic value of GATA3 immunohistochemical determination in BlaCa.…”

Section: Prognostic Valuesupporting

confidence: 89%

“…Considering the higher estrogen levels in females, even after menopause, this observation is aligned with epidemiological data showing less frequent but more aggressive BlaCa in females (24). In the case of GATA3, 10 studies reported expression levels by age and sex (57,65,73,81,86,93,96,98,101), but no significant associations were reported. In the current meta-analysis, GATA3 expression was more frequent in tumours from older patients and, although not significant, there was a trend for higher GATA3 expression in males.…”

Section: Impact Of Age and Sexsupporting

confidence: 69%

“…This agrees with Miyamoto et al (60) that showed a negative correlation between GATA3 and ERb expression. Furthermore, both individual studies and our meta-analysis, propose that ERa and ERb are markers of bad prognosis (33, 36-38, 60, 120), while GATA3 is associated to lower risk of recurrence and more differentiated tumours (60,73,98,115,121). Moreover, while GATA3 is higher in males, ERa appears to be higher in females.…”

Section: Correlation Between Er and Gata3 Positivitymentioning

confidence: 69%

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Association Between Estrogen Receptors and GATA3 in Bladder Cancer: A Systematic Review and Meta-Analysis of Their Clinicopathological Significance

et al. 2021

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BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) and the cooperating protein GATA-binding factor 3 (GATA3) have been implicated in bladder carcinogenesis and tumour progression. GATA3 and ER have been functionally linked in the establishment of luminal fate in breast tissue, but to date their relationship in bladder cancer has not been established. This information will be useful to advance diagnostic and prognostic markers.AimTo determine the relationship between the expression of ERα, ERβ and GATA3 in bladder cancer, disclose their prognostic and diagnostic value and their association with clinicopathological characteristics.MethodsA comprehensive literature search in PubMed database was performed for all immunohistochemical studies of ERα, ERβ and/or GATA3 in bladder cancer patients. We selected eligible studies in accordance with the PRISMA guidelines and evaluated methodological quality and risk of bias based on quality criteria from the reporting recommendations for tumour MARKer (REMARK) prognostic studies. Risk of bias assessment was performed using Review Manager 5. R software was used for all statistical analysis, the packages used were meta and dmetar for the standard meta-analysis, and netmeta for the network meta-analysis.ResultsThirteen studies were eligible for ERα, 5 for ERβ and 58 for GATA3 meta-analysis. Low grade tumours showed significantly lower ERα expression. GATA3 was widely expressed in bladder tumours, especially urothelial carcinomas, with higher expression of GATA3 in low grade and low stage tumours. Data was insufficient to determine the prognostic value of either ERα or ERβ, but GATA3-positivity was associated with higher recurrence free survival. A negative correlation between ERα or ERβ positivity and GATA3 expression was disclosed. Additionally, several sources of heterogeneity were identified, which can be used to improve future studies.ConclusionThe clinicopathological value of ERα and ERβ was inconclusive due to low availability of studies using validated antibodies. Still, this meta-analysis supports GATA3 as good prognostic marker. On the contrary, ERα-positivity was associated to higher grade tumours; while ERα and ERβ were inversely correlated with GATA3 expression. Considering that it has previously been shown that bladder cancer cell lines have functional ERs, this suggests that ERα could be activated in less differentiated cells and independently of GATA3. Therefore, a comprehensive analysis of ERα and ERβ expression in BlaCa supported by complete patient clinical history is required for the identification of BlaCa subtypes and subgroups of patients expressing ERα, to investigate if they could benefit from treatment with hormonal therapy.Systematic Review RegistrationProspero, CRD42021226836.

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Section: Prognostic Valuesupporting

confidence: 89%

Section: Impact Of Age and Sexsupporting

confidence: 69%

Section: Correlation Between Er and Gata3 Positivitymentioning

confidence: 69%

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Association Between Estrogen Receptors and GATA3 in Bladder Cancer: A Systematic Review and Meta-Analysis of Their Clinicopathological Significance

et al. 2021

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“…The luminal tumors may also be further subtyped into uro-like tumors which are p16 negative and genomically unstable tumors which show p16 positivity [33]. The subtypes thus identified have demonstrated significant prognostic and predictive value [24,32].…”

Section: Non-intrinsic Subtypes: P53-like Luminal-infiltrated Stromal-like Infiltrated Claudin-lowmentioning

confidence: 99%

“…Several immunohistochemistry based algorithms have been developed in an attempt to classify bladder cancer into clinically and prognostically significant molecular subtypes [9,10,24,32]. The use of immunohistochemistry as a surrogate to molecular testing shows promise in making molecular subtyping amenable to widespread use.…”

Section: Non-intrinsic Subtypes: P53-like Luminal-infiltrated Stromal-like Infiltrated Claudin-lowmentioning

confidence: 99%

Molecular Classification of Bladder Cancer

Kaushal¹,

Khandakar²

2021

Modern Approach to Diagnosis and Treatment of Bladder Cancer

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Bladder cancer is a biologically and clinically heterogeneous disease. Traditional classification systems, based on pathologic grade, stage and clinical prognosis fail to fully explain how tumors with similar pathology exhibit diverse biological behavior. The introduction of transcriptomics technology has allowed us to catalog all of the mRNA expression patterns and DNA alterations in a given tumor thus expanding our understanding of human cancers. Molecular subtype profiling was attempted only recently in bladder cancer, with the earliest attempts dating back to 2010. Several different molecular classification systems have emerged since. Some of these systems address early bladder cancer, while others focus exclusively on the life-threatening muscle invasive tumors. These molecular subtypes have distinct morphological and clinical characteristics with different therapeutic and prognostic implications, particularly in the era of targeted therapies and immunotherapy. However, molecular subtyping is not without its limitations. Despite the rapidly expanding evidence for important clinical implications, much work is still needed to establish the utility (or lack thereof) of molecular subtyping, and its application in daily practice.

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Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice

et al. 2022

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Prognostic stratification of muscle invasive urothelial carcinomas using limited immunohistochemical panel of Gata3 and cytokeratins 5/6, 14 and 20

Cited by 31 publications

References 39 publications

Association Between Estrogen Receptors and GATA3 in Bladder Cancer: A Systematic Review and Meta-Analysis of Their Clinicopathological Significance

Association Between Estrogen Receptors and GATA3 in Bladder Cancer: A Systematic Review and Meta-Analysis of Their Clinicopathological Significance

Molecular Classification of Bladder Cancer

Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice

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