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Clin Transl Oncol ; 22(7): 1193-1204, 2020 Jul.
Article de Anglais | MEDLINE | ID: mdl-31768922

RÉSUMÉ

PURPOSE: Uveal melanoma (UM) is the most common intraocular cancer with a high mortality rate that requires new research in the field of prevention and treatment. c-REL is a member of the nuclear factor κB (NF-κB) transcription factor family and an emerging regulator of tumorigenesis. Therefore, the objective of the study is to evaluate the constitutive expression of c-REL in uveal melanoma patients and its prognostic significance. METHODS: Detection of c-REL expression was carried out by immunohistochemistry in all 75 patients, and qRT-PCR performed on 58 fresh cases of uveal melanoma along with IL-6 status. Immunoblot was performed to validate immunohistochemistry results. Expression of c-REL protein correlated with clinicopathological parameters and overall survival of patients. RESULTS: Immunohistochemistry results revealed nuclear expression of the c-REL protein (56%) in our cases. Out of 75 cases, 31 cases showed nuclear expression, and 11 cases had cytoplasmic expression. qRT-PCR showed upregulation of the REL gene in 56.89% cases at the transcriptional level. There was a statistically significant difference in the overall survival of patients with c-REL nuclear immunopositivity (p = 0.0048). On multivariate analysis, scleral invasion and c-REL nuclear expression found to be an independent prognostic factor (p < 0.05) CONCLUSIONS: To the best of our knowledge, this was the first study reporting the expression of the c-REL protein in uveal melanoma. Strong nuclear immunoexpression of c-Rel suggests NFκB pathway activation which might be involved in the progression of the disease. Differential expression of c-REL protein may be used as an attractive target for the development of anticancer strategies.


Sujet(s)
Mélanome/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protéines proto-oncogènes c-rel/génétique , Tumeurs de l'uvée/génétique , Adulte , Sujet âgé , Noyau de la cellule/métabolisme , Cytoplasme/métabolisme , Femelle , Humains , Immunohistochimie , Mâle , Mélanome/métabolisme , Mélanome/anatomopathologie , Adulte d'âge moyen , Études prospectives , Protéines proto-oncogènes c-rel/métabolisme , ARN messager/métabolisme , Réaction de polymérisation en chaine en temps réel , RT-PCR , Taux de survie , Tumeurs de l'uvée/métabolisme , Tumeurs de l'uvée/anatomopathologie , NF-kappaB-Inducing Kinase
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