Department of Ophthalmology, Duke University, Durham, North Carolina.
The Permanente Medical Group, San Francisco, California, and.
Retina. 2019 Jun;39(6):1154-1164. doi: 10.1097/IAE.0000000000002113.
To study the relationship between gene expression profile subclass and clinical features in a multicenter cohort of patients with uveal melanoma.
A retrospective, multicenter study was undertaken with patients entered from nine major ocular oncology centers from across the United States. Eligible patients had uveal melanoma and underwent I-125 plaque brachytherapy with concurrent tumor biopsy with gene expression profile testing between January 1, 2010, and October 28, 2014. Data were collected regarding patient demographics, baseline tumor clinical features, and gene expression profile results. Statistical analyses were performed using the Fisher's exact test, Wilcoxon rank-sum test, Kruskal-Wallis test, and proportional-odds cumulative logit modeling.
Inclusion criteria were met for 379 patients. Gene expression profile class divided the cohort into two main groups, Class 1 (n = 263) and Class 2 (n = 113). Class 1 tumors were further subdivided into Class 1a (n = 186) and Class 1b (n = 77). The differences between Class 1 and Class 2 tumors were similar to previous studies, except the finding of Class 2 tumors being more likely to have associated exudative retinal detachment (P < 0.001). There was no statistically significant difference between Class 1 and Class 2 tumors based on the presence of lipofuscin, drusen, or subretinal fluid. Class 1a tumor patients, compared with Class 1b, were significantly older (P = 0.034). Class 2 tumors, when compared with Class 1b, were associated with increasing patient age (P < 0.001), larger tumor height (P = 0.010), ciliary body involvement (P = 0.001), exudative retinal detachment (P = 0.024), and anterior tumor location (P < 0.001). When the tumors were grouped into Collaborative Ocular Melanoma Study size categories, increasing tumor size category was significantly associated with Class 2 status: 6% of small tumors, 32% of medium tumors, and 53% of large tumors were Class 2.
In a multi-institutional setting, we found that the only significant difference in clinical features between Class 1a and Class 1b tumors was that patients with Class 1a tumors were older at the time of diagnosis. We also found that Class 1a and Class 1b have clinical features distinct from Class 2 tumors. The distribution of the gene expression profile subclasses among the size groups was similar to reported time-to-metastasis data among the same size groupings. Our clinical findings support the current molecular classification-based survival data previously reported in uveal melanoma.
研究多中心队列中葡萄膜黑色素瘤患者基因表达谱亚型与临床特征的关系。
这是一项回顾性多中心研究，纳入了 2010 年 1 月 1 日至 2014 年 10 月 28 日期间在美国 9 个主要眼科肿瘤中心接受 I-125 放射性碘 125 瘤内近距离放射治疗联合肿瘤活检的葡萄膜黑色素瘤患者。收集患者的人口统计学资料、基线肿瘤临床特征和基因表达谱检测结果。采用 Fisher 确切检验、Wilcoxon 秩和检验、Kruskal-Wallis 检验和比例优势累积对数模型进行统计学分析。
共纳入 379 例患者，符合纳入标准。基因表达谱分类将队列分为两组，第 1 组（n=263）和第 2 组（n=113）。第 1 组肿瘤进一步细分为第 1a 组（n=186）和第 1b 组（n=77）。第 1 组和第 2 组肿瘤之间的差异与之前的研究相似，但第 2 组肿瘤更可能伴有渗出性视网膜脱离（P<0.001）。第 1 组和第 2 组肿瘤之间在脂褐素、玻璃膜疣或视网膜下液的存在方面无统计学差异。与第 1b 组相比，第 1a 组肿瘤患者的年龄明显更大（P=0.034）。与第 1b 组相比，第 2 组肿瘤与患者年龄的增加相关（P<0.001）、肿瘤高度更大（P=0.010）、睫状体受累（P=0.001）、渗出性视网膜脱离（P=0.024）和前位肿瘤位置（P<0.001）。当将肿瘤分为 COMS 大小类别时，肿瘤大小类别的增加与第 2 类状态显著相关：小肿瘤的 6%、中肿瘤的 32%和大肿瘤的 53%为第 2 类。
在多机构环境中，我们发现第 1a 组和第 1b 组肿瘤之间唯一显著的临床特征差异是第 1a 组患者的诊断时年龄更大。我们还发现第 1a 组和第 1b 组与第 2 组肿瘤具有不同的临床特征。基因表达谱亚类在大小组中的分布与同一大小组中转移时间的报告数据相似。我们的临床发现支持之前在葡萄膜黑色素瘤中报告的基于当前分子分类的生存数据。
