Uveal melanoma is the most common primary intraocular malignancy in adults. Almost half of patients with uveal melanoma may die from metastatic disease and the most frequent site of metastases is the liver. It is considered as an inflammatory phenotype. NFκB plays a connecting link between the inflammation and cancer. c-Rel and p50 are together considered as a heterodimer (c-Rel/p50) which plays an important role in inflammation and cancer progression. Therefore, the aim of the study is to detect c-Rel/p50 heterodimer expression in the tumour microenvironment of uveal melanoma and its prognostic significance.
Evaluation of c-Rel/p50 heterodimer expression was performed in 75 formalin fixed uveal melanoma tissues by using immunohistochemistry. Transcriptional analysis was performed on 58 fresh tissues by real-time PCR (q-PCR). Co-Immunoprecipitation (Co-IP) was done on 10 representative cases to assess the presence of c-Rel/p50 heterodimer and validation of immunohistochemistry results was performed by western blotting. Results were then correlated with clinicopathological parameters.
Immunoexpression of c-Rel+/p50+ is localized to the cytoplasm in normal choroid whereas both cytoplasmic and nuclear expression was seen in 33.33% cases. At the transcriptional level, upregulation of c-Rel+/p50+ heterodimer was shown in 43.10%. Expression of both cytoplasmic and nuclear c-Rel+/p50+ heterodimer were found to have significant correlation with cases having tumour infiltrating lymphocytes, macrophages (CD68+) and high pigmentation. There was a statistically significant difference in the overall survival of patients with nuclear and cytoplasmic expression of c-Rel+/p50+ heterodimer (p < 0.05).
We conclude that c-Rel+/p50+ heterodimer may be used as a poor prognostic indicator of survival outcome in uveal melanoma. Further translational and validation studies are required to confirm its usage as a therapeutic drug target in metastatic uveal melanoma.
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