Constitutive expression of c‑REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome

• M. K. Singh ^[1] ; L. Singh ^[2] ; N. Pushker ^[3] ; K. Chosdol ^[4] ; S. Bakhshi ^[5] ; R. Meel ^[3] ; S. Sen ^[1] ; S. Kashyap ^[1]
  1. [1] Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  2. [2] Departrment of Biosciences, JMI, New Delhi, India
  3. [3] Department of Ophthalmology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  4. [4] Department of Biochemistry, AIIMS, New Delhi, India
  5. [5] Department of Medical Oncology, IRCH, AIIMS, New Delhi, India

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 7, 2020, págs. 1193-1204
• Idioma: inglés
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• Resumen

  • 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