Publication date: May 08, 2019
Inflammation in uveal melanoma (UM) is linked to a bad prognosis. It is rare type of cancer, of which the metastases are usually fatal within a year. Infiltration with an inflammatory infiltrate increases with disease progression but does not seem to inhibit metastasis. The Canonical NF_705B (C-NF_705B) pathway is known to play a crucial role in tumor inflammation. We therefore, studied the expression of canonical NF_705B proteins and their prognostic relevance in UM. Our study evaluated the expression of C-NF_705B proteins (p65, p50, and c-Rel) by using immunohistochemistry on sections from 75 formalin-fixed UM. Activation of the NF_705B subunit was determined on fresh tumor specimens by measuring the DNA-binding activity in nuclei using an NF_705B ELISA assay. Real-time PCR was performed on frozen material on 58 tumors. The presence of native C-NF_705B heterodimers (p65/p50 and c-Rel/p50) was confirmed by co-immunoprecipitation followed by Western blotting. We observed a high nuclear immunoreactivity of p65, p50, and c-Rel proteins in 54, 60 and 41% UM cases, respectively. Expression of C-NF_705B proteins significantly correlated with parameters which are related to the inflammatory environment of UM. Nuclear immunoreactivity of p65 and p50 was associated with lower patient survival (p = 0.041; p = 0.048) while c-Rel was not. Our finding reveals that C-NF_705B proteins expressed are more often in UM with inflammation than those without inflammation. Activation of the canonical NF_705B pathway is more frequent in high risk UM patients. These observations might help to understand the behaviour of high risk tumors, with upregulation of C-NF_705B proteins contributing to tumor aggressiveness.
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