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.

色素沉着的生物学理解及其与葡萄膜黑色素瘤（UM）风险的临床病理学意义之间的联系尚待探索。包含E3泛素蛋白连接酶2（HERC2）和粉红眼稀释蛋白（P蛋白）的HECT和RLD域是调节眼睛色素沉着的重要标志。因此，我们的研究目的是研究UM患者中HERC2和P蛋白的表达，并与患者预后相关。纳入五十二份福尔马林固定石蜡包埋的UM组织样品，通过免疫组织化学检测HERC2和P蛋白的表达，并通过Western blot验证。使用Cox比例风险模型和对数秩检验确定这些蛋白质的预后潜力。在67％的UM病例中观察到高色素沉着。HERC2和P蛋白的表达分别存在于44％和71％的病例中。经统计学分析，色素沉着增加，上皮样细胞类型和睫状体浸润与蛋白表达显着相关（p  ＜0.05）。表达HERC2和P蛋白的UM患者无转移生存率降低。在多变量分析中，发现P蛋白表达是独立的预后因素。我们的发现表明，在具有高转移潜力的UM病例中，HERC2和P蛋白可用作高色素沉着的新型预测因子。