Clinical significance of epithelial-to-mesenchymal transition in laryngeal carcinoma: Its role in the different subsites

Mezi, Silvia; Chiappetta, Caterina; Carletti, Raffaella; Nardini, Andrea; Cortesi, Enrico; Orsi, Errico; Piesco, Gabriele; Gioia, Cira Di

doi:10.1002/hed.24838

Cited by 15 publications

(11 citation statements)

References 40 publications

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“…The IHC evaluation for each antibody was performed by 2 experienced investigators who analyzed the immunostaining in the entire tumor area present in the slide (at magnification 20×). Results were expressed with a semiquantitative double score based on staining localization (nuclear or cytoplasmic) and intensity (negative, weak, moderate, strong) [31].…”

Section: Protein Expression Analysesmentioning

confidence: 99%

Loss of Function SETD2 Mutations in Poorly Differentiated Metastases from Two Hürthle Cell Carcinomas of the Thyroid

Pecce

Verrienti

Abballe

et al. 2020

Cancers

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Hürthle cell carcinomas (HCC) are rare differentiated thyroid cancers that display low avidity for radioactive iodine and respond poorly to kinase inhibitors. Here, using next-generation sequencing, we analyzed the mutational status of primary tissue and poorly differentiated metastatic tissue from two HCC patients. In both cases, metastatic tissues harbored a mutation of SETD2, each resulting in loss of the SRI and WW domains of SETD2, a methyltransferase that trimethylates H3K36 (H3K36me3) and also interacts with p53 to promote its stability. Functional studies of the novel p.D1890fs6* mutation (case 1) revealed significantly reduced H3K36me3 levels in SETD2-mutated tissue and primary cell cultures and decreased levels of the active form of p53. Restoration of SETD2-wildtype expression in the SETD2-mutant cells significantly reduced the expression of four well-known stemness markers (OCT-4, SOX2, IPF1, Goosecoid). These findings suggest potential roles for SETD2 loss-of-function mutations in HCC progression, possibly involving p53 destabilization and promotion of stemness. Their prevalence and potential treatment implications in thyroid cancer, especially HCC, require further study.

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Section: Protein Expression Analysesmentioning

confidence: 99%

Loss of Function SETD2 Mutations in Poorly Differentiated Metastases from Two Hürthle Cell Carcinomas of the Thyroid

Pecce

Verrienti

Abballe

et al. 2020

Cancers

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“…Furthermore, E‐cadherin is also a key molecule involved in epithelial‐mesenchymal transition process, which is the hallmark for cancer metastasis. Researchers found that epithelial‐mesenchymal transition resulting from E‐cadherin loss contributed to invasion and metastasis of human tumors . The E‐cadherin loss with epithelial‐mesenchymal transition also promoted radioresistance in human tumor cells .…”

Section: Discussionmentioning

confidence: 99%

“…Researchers found that epithelialmesenchymal transition resulting from E-cadherin loss contributed to invasion and metastasis of human tumors. [37][38][39] The E-cadherin loss with epithelial-mesenchymal transition F IGUR E 4 Sensitivity analysis for the pooled odds ratios with confidence interval (CIs) of the association between E-cadherin methylation and nasopharyngeal carcinoma risk. Results were computed by omitting each study in turn.…”

Section: Discussionmentioning

confidence: 99%

Association of E‐cadherin methylation with risk of nasopharyngeal cancer: A meta‐analysis

Peng

Sun

et al. 2018

Head & Neck

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“…This transition is thought to be associated with cellular plasticity and loss of the epithelial adhesion marker, E-cadherin, and gain in expression of mesenchymal markers such as N-cadherin and vimentin [5,6–8]. These changes have been termed “cadherin switching” and have been associated with poor prognosis [4,7, 9–12]. EMT is also a characteristic of cancer initiating stem cells that may be responsible for tumor recurrence and treatment resistance [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Although EMT is a characteristic of increased motility and invasiveness, it remains unclear if EMT and tumor “stemness” are associated with the host immune response or immunosuppression in the tumor microenvironment [4,28,29]. The relationship of markers of EMT and potentially important prognostic factors such as pattern of invasion [30–33] and tumor infiltrating lymphocytes [34–38] remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck

et al. 2018

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Introduction: Disruption of E-cadherin function and increased expression of vimentin and the transcriptional oncogene, SOX2, are thought to characterize epithelial to mesenchymal transition (EMT) in HNSCC that contributes to invasive and metastatic behavior. To determine if such changes relate to prognosis or host immune response, expression of these markers and correlations with clinical characteristics, histologic worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TIL) and survival were assessed. Methods: Immunohistologic expression of markers was determined in tissue microarrays from 274 previously untreated HNSCC patients. Expression was correlated with levels of TILs in microcores and WPOI in biopsy specimens. Correlations were assessed by Kruskal-Wallis testing and Spearman correlation coefficients where appropriate. Overall and relapse-free survival were analyzed with Cox proportional hazards models. Median follow up was 60.0 months. Results: Loss of E-cadherin expression was significantly associated with low or absent SOX2 expression (R=0.433, p<0.0001). SOX2 expression and low grade WPOI were significantly associated with favorable overall (OS) and relapse free (RFS) survival in multivariable analysis. E-cadherin expression did not correlate with TILs, however WPOI score correlated indirectly with CD4, CD8, and FoxP3 levels. When grouped by primary treatment, lower grades (1,2) of WPOI predicted improved RFS and OS in patients treated with primary surgery but not for patients treated with chemoradiation. Conclusion: The findings suggest that SOX2 expression and WPOI are significant prognostic factors and that WPOI correlates with decreased T cell infiltration. The combination of markers and TILs might be useful in selecting patients for primary surgery.

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Clinical significance of epithelial-to-mesenchymal transition in laryngeal carcinoma: Its role in the different subsites

Abstract: The negative prognostic role of epithelial-to-mesenchymal transition has been confirmed and a predictive role in glottic tumors has been suggested, leading us to propose epithelial-to-mesenchymal transition as an additional adverse feature in laryngeal carcinoma.

Cited by 15 publications

References 40 publications

Loss of Function SETD2 Mutations in Poorly Differentiated Metastases from Two Hürthle Cell Carcinomas of the Thyroid

Loss of Function SETD2 Mutations in Poorly Differentiated Metastases from Two Hürthle Cell Carcinomas of the Thyroid

Association of E‐cadherin methylation with risk of nasopharyngeal cancer: A meta‐analysis

Histologic pattern of invasion and epithelial-mesenchymal phenotype predict prognosis in squamous carcinoma of the head and neck

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