Abstract
Biological understanding of pigmentation and its association with clinicopathological implications in uveal melanoma (UM) risk is still unexplored. HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 2 (HERC2) and Pink-eyed dilution protein (P-protein) are the important markers that regulate pigmentation in eye. Therefore, our aim of the study was to investigate the expression of HERC2 and P-protein in the UM patients and correlate with patient outcome. Fifty-two formalin-fixed paraffin-embedded UM tissue samples were included to detect the expression of HERC2 and P-protein by immunohistochemistry and validated by western blot. Cox proportional hazard model and log-rank test were used to determine the prognostic potential of these proteins. High pigmentation was seen in 67% of the UM cases. The expression of HERC2 and P-protein was present in 44% and 71% cases, respectively. On statistical analysis, increased pigmentation, epithelioid cell type, and ciliary body invasion were significant with the protein expressions (p < 0.05). Metastasis-free survival was reduced in UM cases which expressed HERC2 and P-protein. On multivariate analysis, P-protein expression was found to be an independent prognostic factor. Our findings suggest that HERC2 and P-protein could be used as novel predictors of high pigmentation in UM cases which have high metastatic potential.
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This research was funded by Intramural Research Grant (IRG), All India Institute of Medical Sciences, New Delhi (F.8-636/A-636/2018/RS).
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This research involved the human participants. All procedures were approved by the institutional ethics committee, All India Institute of Medical Sciences (AIIMS), New Delhi, India (IEC-472/07.09.2018).
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Kashyap, S., Singh, M.K., Jha, J. et al. Prognostic impact of HERC2 protein and pink-eyed dilution protein in uveal melanoma. Human Cell 33, 1264–1272 (2020). https://doi.org/10.1007/s13577-020-00397-9
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DOI: https://doi.org/10.1007/s13577-020-00397-9