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DOI: 10.14670/HH-11-778
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Título: | An immunohistochemical study of NFE2L2, KEAP1 and 8-hydroxy-2'-deoxyguanosine and the EMT markers SNAI2, ZEB1 and TWIST1 in metastatic melanoma |
Fecha de publicación: | 2017 |
Editorial: | Universidad de Murcia. Departamento de Biología Celular e Histología |
Cita bibliográfica: | Histology and Histopathology, Vol.32, nº2, (2017) |
ISSN: | 1699-5848 0213-3911 |
Materias relacionadas: | CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología |
Palabras clave: | EMT Melanoma NFE2L2 Reactive oxygen species 8-hydroxy-2'-deoxyguanosine |
Resumen: | Background: Little is known regarding the role of redox balance regulators in metastatic melanomas, but there is some evidence for a link between epithelial-to-mesenchymal transition (EMT) and cellular redox status. Methods: We compared the immunohistochemical expression of nuclear factor erythroid-2-related factor 2 (NFE2L2), Kelch-like ECH-associated protein 1 (KEAP1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), TWIST1, SNAI2 and ZEB1 between primary melanomas and metastases in a cohort of 23 nevi, 66 malignant melanomas and 22 metastases. Results: Nuclear NFE2L2 expression was higher (p=0.003) and cytoplasmic KEAP1 lower (p=0.026) in metastatic lesions than at primary sites. Nuclear NFE2L2 expression was associated with the presence of distant metastases (p=0.040) and with nuclear TWIST1 expression (p=0.002). Patients having both NFE2L2 and TWIST1 expression in nuclei had an extremely poor prognosis (p=0.0003). In multivariate analysis nuclear TWIST1 expression was an independent predictor of a poorer prognosis (HR 2.99, 95% CI 1.17-7.69; p=0.023) and the invasive TWIST1/ZEB1 phenotype showed poorer melanoma-specific survival (HR 7.28, 95% CI 2.23-23.77; p=0.001). Nuclear expression of 8-OHdG (p=0.001) was lower at metastatic sites than in primary lesions. Conclusions: EMT signalling and the KEAP1/NFE2L2- axis are likely to be involved in metastatic spread of malignant melanoma and also appear to have potential interactions. |
Autor/es principal/es: | Hintsala, Hanna Riikka Haapasaari, Kirsi Maria Soini, Ylermi Karihtala, Peeter |
URI: | http://hdl.handle.net/10201/116743 |
DOI: | DOI: 10.14670/HH-11-778 |
Tipo de documento: | info:eu-repo/semantics/article |
Número páginas / Extensión: | 8 |
Derechos: | info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
Aparece en las colecciones: | Vol.32, nº2 (2017) |
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