Purpose

Individuals with gray, blue, or green eyes have a higher chance of developing uveal melanoma (UM) than those with brown eyes. We wondered whether iris pigmentation might be related not only to predisposition to UM but also to its behavior; therefore, we compared the clinical, histopathologic, and genetic characteristics of UM between eyes with different colors.

Design

We determined iris color in a large cohort of patients enucleated for UM. Clinical and histopathologic tumor characteristics, chromosome status, and survival were compared among 3 groups on the basis of iris color.

Participants

A total of 412 patients with choroidal/ciliary body UM, who had undergone primary enucleation at the Leiden University Medical Center, Leiden, The Netherlands, between 1993 and 2019, were divided into 3 groups based on iris color: gray/blue, green/hazel, and brown. The validation cohort included 934 patients with choroidal/ciliary body UM treated at Wills Eye Hospital (WEH).

Methods

Comparison of clinical, histopathologic, and genetic characteristics of UM in patients with different iris colors.

Main Outcome Measures

Melanoma-related survival in UM patients, divided over 3 iris color groups, in relation to the tumor’s chromosome 3 and 8q status.

Results

Moderate and heavy tumor pigmentations were especially seen in eyes with a brown iris (P < 0.001). Survival did not differ between patients with different iris colors (P = 0.27); however, in patients with a light iris, copy number changes in chromosome 3 and 8q had a greater influence on survival than in patients with a dark iris. Likewise, chromosome 3 and chromosome 8q status affected survival more among patients with lightly pigmented tumors than in patients with heavily pigmented tumors. The WEH cohort similarly showed a greater influence of chromosome aberrations in light-eyed individuals.

Conclusions

Although iris color by itself did not relate to UM-related survival, chromosome 3 and 8q aberrations had a larger influence on survival in patients with a light iris than those with a brown iris. This suggests a synergistic effect of iris pigmentation and chromosome status in the regulation of oncogenic behavior of UM. Iris color should be taken into consideration when calculating a patient's risk for developing metastases.

中文翻译：

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葡萄膜黑色素瘤中的染色体 3 和 8q 畸变对虹膜浅色与深虹膜颜色患者的生存影响更大

目的

灰色、蓝色或绿色眼睛的人比棕色眼睛的人更容易患上葡萄膜黑色素瘤 (UM)。我们想知道虹膜色素沉着是否不仅与 UM 的易感性有关，还与它的行为有关；因此，我们比较了不同颜色眼睛之间 UM 的临床、组织病理学和遗传特征。

设计

我们在一大群因 UM 摘除的患者中确定了虹膜颜色。根据虹膜颜色比较3组的临床和组织病理学肿瘤特征、染色体状态和生存率。

参与者

1993 年至 2019 年期间在荷兰莱顿莱顿大学医学中心接受初级摘除的 412 名脉络膜/睫状体 UM 患者，根据虹膜颜色分为 3 组：灰色/蓝色、绿色/淡褐色和棕色。验证队列包括在 Wills 眼科医院 (WEH) 治疗的 934 名脉络膜/睫状体 UM 患者。

方法

不同虹膜颜色患者 UM 临床、组织病理学和遗传特征的比较。

主要观察指标

UM 患者的黑色素瘤相关存活率，分为 3 个虹膜颜色组，与肿瘤的 3 号染色体和 8q 状态有关。

结果

中度和重度肿瘤色素沉着在虹膜棕色的眼睛中尤为明显（P < 0.001）。不同虹膜颜色的患者存活率无差异（P  = 0.27）；然而，在虹膜浅的患者中，3 号和 8q 染色体的拷贝数变化对生存的影响比虹膜深的患者更大。同样，3 号染色体和 8q 号染色体状态对轻度色素沉着肿瘤患者的生存率的影响比重度色素沉着肿瘤患者更大。WEH 队列同样显示出染色体畸变对浅色个体的更大影响。

结论

尽管虹膜颜色本身与 UM 相关的存活率无关，但 3 号和 8q 染色体畸变对虹膜浅色患者的存活率影响大于棕色虹膜患者的存活率。这表明虹膜色素沉着和染色体状态在调节 UM 的致癌行为中具有协同作用。在计算患者发生转移的风险时，应考虑虹膜颜色。