Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?

Bulzico, Daniel; Faria, Paulo Antônio Silvestre de; Maia, Camila Bravo; Paula, Marcela Pessoa de; Torres, Davi Coe; Ferreira, Gerson Moura; Pires, Bruno R. B.; Hassan, Rocı́o; Abdelhay, Eliana; Neto, Leonardo Vieira

doi:10.1007/s12020-017-1409-z

Cited by 7 publications

(7 citation statements)

References 64 publications

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“…In this study we investigated a series of both classical epithelial and mesenchymal markers in a large cohort of normal, benign and malignant adrenocortical tissues, and compared the expression of these markers with that in epithelial and mesenchymal control tissues. Against our hypothesis, our analysis revealed that in adrenocortical tumors EMT indicated by a more frequent occurrence of mesenchymal markers in neoplastic tissue, does not appear to play a role in tumor progression as suggested before in smaller studies [28,29]. Adrenocortical tissues do not express established epithelial markers like E-cadherin and EpCAM but express a series of "classical" mesenchymal markers like Slug and N-cadherin at similar levels as mesenchymal tissues.…”

Section: Discussionsupporting

confidence: 64%

“…Accordingly, adrenal tumors are also classified as carcinomas (tumors of an epithelial tissue) [26] as opposed to sarcomas (tumors of a mesenchymal tissue) [27]. Two studies have provided a first indication that adrenocortical tissues are expressing some mesenchymal markers [28,29]. However, the number of adrenocortical carcinoma tissues analyzed in these studies was low (24 cases in each study) and a correlation between EMT marker expression and clinicopathological markers indicative of tumor aggressiveness was not possible.…”

Section: Introductionmentioning

confidence: 99%

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Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?

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Kircher

Altieri

et al. 2021

Cancers

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A clinically relevant proportion of adrenocortical carcinoma (ACC) cases shows a tendency to metastatic spread. The objective was to determine whether the epithelial to mesenchymal transition (EMT), a mechanism associated with metastasizing in several epithelial cancers, might play a crucial role in ACC. 138 ACC, 29 adrenocortical adenomas (ACA), three normal adrenal glands (NAG), and control tissue samples were assessed for the expression of epithelial (E-cadherin and EpCAM) and mesenchymal (N-cadherin, SLUG and SNAIL) markers by immunohistochemistry. Using real-time RT-PCR we quantified the alternative isoform splicing of FGFR 2 and 3, another known indicator of EMT. We also assessed the impact of these markers on clinical outcome. Results show that both normal and neoplastic adrenocortical tissues lacked expression of epithelial markers but strongly expressed mesenchymal markers N-cadherin and SLUG. FGFR isoform splicing confirmed higher similarity of adrenocortical tissues to mesenchymal compared to epithelial tissues. In ACC, higher SLUG expression was associated with clinical markers indicating aggressiveness, while N-cadherin expression inversely associated with these markers. In conclusion, we could not find any indication of EMT as all adrenocortical tissues lacked expression of epithelial markers and exhibited closer similarity to mesenchymal tissues. However, while N-cadherin might play a positive role in tissue structure upkeep, SLUG seems to be associated with a more aggressive phenotype.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?

Sbiera

Kircher

Altieri

et al. 2021

Cancers

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“…Although their expression was inversely proportional, no association was observed between Twist1 and E-cadherin mRNA levels. These data corroborate our group's previous findings, as we demonstrated low levels of E-cadherin in all types of adrenocortical tumors through immunohistochemistry (8).…”

Section: Resultssupporting

confidence: 93%

“…Furthermore, Waldmann et al (7) reported an increased expression of Snail1, another EMT-related transcription factor, in 26 cases of ACC in comparison to 12 cases of adrenal adenomas. Recently, our group originally described that Twist1 protein expression is significantly increased in malignant adrenocortical tumors in both adult and childhood onset scenarios (8). Moreover, we found that the protein levels of the EMT marker vimentin were significantly increased in the most aggressive tumors, and that this increase was directly correlated to Twist1 expression.…”

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confidence: 57%

Twist1 Correlates With Epithelial-Mesenchymal Transition Markers Fibronectin and Vimentin in Adrenocortical Tumors

et al. 2018

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Background/Aim: Although the knowledge regarding adrenocortical carcinomas (ACC) tumorigenesis has significantly improved during the last decade, it still remains to be completely determined. Epithelialmesenchymal transition (EMT) is a well described transcription factor induced process, postulated as an essential step toward cancer progression and metastasis development. In this context, Twist1 has been described as the EMT master-regulator. The aim of this study was to assess the association among Twist1, fibronectin, vimentin and Ecadherin gene expression in adrenocortical tumor samples. Materials and Methods: Twist1, fibronectin, vimentin and Ecadherin gene expression in 18 adrenal adenomas, 18 ACC, and 24 childhood onset adrenocortical tumors were assessed in formalin-fixed paraffin-embedded tissues. The fold expression was calculated according to the 2 ΔCt method. Results: A significant correlation between mRNA levels of Twist1, fibronectin and vimentin was evident. Although their expression was inversely proportional, no association was observed between Twist1 and E-cadherin expression. Conclusion: The expression of Twist1, the major regulator of EMT, is directly correlated to the expression of mesenchymal markers fibronectin and vimentin in ACC samples.

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“…Increasing evidence suggests that the epithelial-mesenchymal transition (EMT) may participate in adrenal tumourigenesis. According to those reports, EMT markers (E−/P−/N-cadherins, vimentin, fibronectin, MMP-2/− 9 and caveolin-1), and downstream transcriptional regulators (TWIST1, SIP1, Snail, ZEB-1/− 2, Slug) were all found to be dysregulated and associated with poor prognosis [12–14]. These results indicate a potential role of EMT in the development of ACC.…”

Section: Introductionmentioning

confidence: 97%

Expression of FSCN1 and FOXM1 are associated with poor prognosis of adrenocortical carcinoma patients

et al. 2019

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BackgroundAdrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs.MethodsClinical and specimen data from 130 adrenocortical carcinoma (ACC) patients was acquired from the Cancer Genome Atlas (TCGA) database (n = 79) and a West China Hospital (WCH) cohort (n = 51). In the WCH cohort, archived formalin-fixed paraffin embedded (FFPE) samples were collected for immunohistochemical analysis. The correlation between the EMT genes and the tumour microenvironment status was estimated based on the Tumour Immune Estimation Resource (TIMER) algorithm. Kaplan-Meier analysis, followed by univariate and multivariate regression analyses, were performed to identify the prognostic association of FSCN1 and FOXM1.ResultsFSCN1 and FOXM1 were over-expressed in ACC tissue when compared with adrenocortical adenoma and normal adrenal tissue. Over-expression of FSCN1 or FOXM1 was associated with the tumour microenvironment and immune signatures in ACCs. Patients with higher expression of FSCN1 or FOXM1 were more likely to have worse prognoses. The prognostic effects were further verified in both early (stage I/II) and advanced (stage III/IV) ACCs. Furthermore, FSCN1 and FOXM1 appeared as independent prognostic factors in ACC.ConclusionsThese results show that FSCN1 and FOXM1 are independent prognostic factors in ACCs and over-expression of FSCN1 or FOXM1 indicates a worse prognosis.

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Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?

Abstract: Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.

Cited by 7 publications

References 64 publications

Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?

Epithelial and Mesenchymal Markers in Adrenocortical Tissues: How Mesenchymal Are Adrenocortical Tissues?

Twist1 Correlates With Epithelial-Mesenchymal Transition Markers Fibronectin and Vimentin in Adrenocortical Tumors

Expression of FSCN1 and FOXM1 are associated with poor prognosis of adrenocortical carcinoma patients

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