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08.05.2019 | Research Paper | Ausgabe 3/2019

Clinical & Experimental Metastasis 3/2019

Identification of canonical NFκB (C-NFκB) pathway in uveal melanoma and their relation with patient outcome

Zeitschrift:
Clinical & Experimental Metastasis > Ausgabe 3/2019
Autoren:
Mithalesh Kumar Singh, Lata Singh, Neelam Pushker, Neeru Saini, Rachna Meel, Kunzang Chosdol, Sameer Bakhshi, Seema Sen, Pradeep Venkatesh, Bhavna Chawla, Jasbir Kaur, Seema Kashyap
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The online version of this article (https://​doi.​org/​10.​1007/​s10585-019-09969-y) contains supplementary material, which is available to authorized users.

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Abstract

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 NFκB (C-NFκB) pathway is known to play a crucial role in tumor inflammation. We therefore, studied the expression of canonical NFκB proteins and their prognostic relevance in UM. Our study evaluated the expression of C-NFκB proteins (p65, p50, and c-Rel) by using immunohistochemistry on sections from 75 formalin-fixed UM. Activation of the NFκB subunit was determined on fresh tumor specimens by measuring the DNA-binding activity in nuclei using an NFκB ELISA assay. Real-time PCR was performed on frozen material on 58 tumors. The presence of native C-NFκB 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-NFκB 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-NFκB proteins expressed are more often in UM with inflammation than those without inflammation. Activation of the canonical NFκB 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-NFκB proteins contributing to tumor aggressiveness.

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Zusatzmaterial
Supplementary material 1—Supplementary Figure 1 a Nuclear Immunoreactivity patterns of C-NFκB proteins uveal melanoma; b Relative immunoreactivity patterns of C-NFκB proteins in group I and group II uveal melanoma (TIFF 132 kb)
10585_2019_9969_MOESM1_ESM.tif
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