M.K. Singh, L. Singh, N. Pushker, K. Chodsol, S. Bakhshi, R. Meel, S. Sen, S. Kashyap
PurposeUveal 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.MethodsDetection of c-REL expression was carried out by immunohistochemistry in all 75 patients, and qRT-PCR per-formed on 58 fresh cases of uveal melanoma along with IL-6 status. Immunoblot was performed to validate immunohisto-chemistry results. Expression of c-REL protein correlated with clinicopathological parameters and overall survival of patients.ResultsImmunohistochemistry 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 RELgene 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)ConclusionsTo 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
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