Uveal melanomas are considered as malignant phenotype having a high density of macrophages, blood vessels, and T-lymphocytes. Presence of epithelioid cells with high melanin pigmentation leads to worse patient's prognosis. Non-canonical NFκB (NC-NFκB) pathway plays an important role in inflammation which promotes cancer initiation and progression. p52 and RelB are the dimer proteins of the NC-NFκB pathway. The aim of the study is to detect the expression of p52/RelB protein dimer in the inflammatory microenvironment of uveal melanoma and its prognostic significance.
Evaluation of p52/RelB dimer was assessed by using immunohistochemistry and western blotting in 75 formalin fixed uveal melanoma tissues and transcriptional analysis was done on 58 fresh frozen tissues by real-time PCR. Immunopositive expression of both proteins was taken as a positive expression of the dimer (p52+/RelB+) and immunonegative of both proteins taken as (p52-/RelB-) negative expression of the dimer. Results were then correlated with clinicopathological parameters and disease-free survival.
Immunoexpression of p52+/RelB+ protein showed both nuclear and cytoplasmic expression in 35 cases whereas 15 showed cytoplasmic only. qRT-PCR showed upregulation of p52+/RelB+ gene in 65.51% cases at the transcriptional level. Expression of both cytoplasmic and nuclear p52+/RelB+ dimers showed significant correlation with cases having high tumor infiltrated lymphocytes, macrophages (CD68+) and presence of blood vessels (CD34+). There was a statistically significant difference in the disease-free survival of patients with nuclear/cytoplasmic p52+/RelB+ immunopositivity (p < 0.05).
This preliminary data suggests that p52/RelB protein dimer plays an important role in the inflammatory microenvironment of uveal melanoma which might be responsible for the pathogenesis of this disease. Further translational studies are required to explore the nature of NC-NFκB pathway in the tumor microenvironment of uveal melanoma.
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