Wierenga Annemijn P A, Brouwer Niels J, Gelmi Maria Chiara, Verdijk Robert M, Stern Marc-Henri, Bas Zeynep, Malkani Kabir, van Duinen Sjoerd G, Ganguly Arupa, Kroes Wilma G M, Marinkovic Marina, Luyten Gregorius P M, Shields Carol L, Jager Martine J
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Section Ophthalmic Pathology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Ophthalmology. 2022 Apr;129(4):421-430. doi: 10.1016/j.ophtha.2021.11.011. Epub 2021 Nov 13.
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.
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.
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).
Comparison of clinical, histopathologic, and genetic characteristics of UM in patients with different iris colors.
Melanoma-related survival in UM patients, divided over 3 iris color groups, in relation to the tumor's chromosome 3 and 8q status.
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.
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.
与棕色眼睛的人相比，拥有灰色、蓝色或绿色眼睛的人患葡萄膜黑色素瘤（UM）的几率更高。我们想知道虹膜色素沉着是否不仅与UM的易感性有关，还与其行为有关；因此，我们比较了不同颜色眼睛的UM患者的临床、组织病理学和基因特征。
我们在一大群因UM而摘除眼球的患者中确定了虹膜颜色。根据虹膜颜色将3组患者的临床和组织病理学肿瘤特征、染色体状态及生存率进行了比较。
1993年至2019年间在荷兰莱顿大学医学中心接受初次眼球摘除术的412例脉络膜/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。验证队列包括在威尔斯眼科医院（WEH）接受治疗的934例脉络膜/睫状体UM患者。
比较不同虹膜颜色患者UM的临床、组织病理学和基因特征。
UM患者的黑色素瘤相关生存率，根据肿瘤的3号和8号染色体q臂状态分为3个虹膜颜色组。
中度和重度肿瘤色素沉着尤其多见于棕色虹膜的眼睛（P<0.001）。不同虹膜颜色患者的生存率无差异（P=0.27）；然而，虹膜颜色浅的患者中，3号染色体和8号染色体q臂的拷贝数变化对生存率的影响大于虹膜颜色深的患者。同样，在色素沉着浅的肿瘤患者中，3号染色体和8号染色体q臂状态对生存率的影响大于色素沉着重的肿瘤患者。WEH队列同样显示，染色体畸变对浅色眼睛个体的影响更大。
虽然虹膜颜色本身与UM相关生存率无关，但3号染色体和8号染色体q臂畸变对虹膜颜色浅的患者生存率的影响大于棕色虹膜患者。这表明虹膜色素沉着和染色体状态在调节UM致癌行为方面具有协同作用。在计算患者发生转移的风险时，应考虑虹膜颜色。
