Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Suite, Philadelphia, PA, United States.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
Indian J Ophthalmol. 2019 Dec;67(12):1959-1963. doi: 10.4103/ijo.IJO_1589_19.
The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus (vs.) TCGA.
Review of published reports on AJCC and TCGA classification for UM was performed. Outcomes based on AJCC 7 and 8 editions were assessed. For TCGA, UM was classified based on chromosomes 3 and 8 findings including disomy 3 (D3), monosomy 3 (M3), disomy 8 (D8), 8q gain (8qG), or 8q gain multiple (8qGm) and combined into four classes including Class A (D3/D8), Class B (D3/8qG), Class C (M3/8qG), and Class D (M3/8qGm). Outcomes of metastasis and death were explored and a comparison (AJCC vs. TCGA) was performed.
In the NCI CCG study, there were 80 eyes with UM sampled by enucleation (n = 77), resection (n = 2), or orbitotomy (n = 1) and analysis revealed four distinct genetic classes. Metastasis and death outcomes were subsequently evaluated per class in the WEH study. The WEH study reviewed 658 eyes with UM, sampled by FNAB, and found Class A (n = 342, 52%), B (n = 91, 14%), C (n = 118, 18%), and D (n = 107, 16%). Comparison by increasing class (A vs. B vs. C vs. D) revealed older mean patient age (P < 0.001), worse entering visual acuity (P < 0.001), greater distance from the optic disc (P < 0.001), larger tumor diameter (P < 0.001), and greater tumor thickness (P < 0.001). Regarding outcomes, more advanced TCGA class demonstrated increased 5-year risk for metastasis (4% vs. 20% vs. 33% vs. 63%,P < 0.001) with corresponding increasing hazard ratio (HR) (1.0 vs. 4.1, 10.1, 30.0,P= 0.01 for B vs. A andP < 0.001 for C vs. A and D vs. A) as well as increased 5-year estimated risk for death (1% vs. 0% vs. 9% vs. 23%,P < 0.001) with corresponding increasing HR (1 vs. NA vs. 3.1 vs. 13.7,P= 0.11 for C vs. A andP < 0.001 for D vs. A). Comparison of AJCC to TCGA classification revealed TCGA was superior in prediction of metastasis and death from UM.
TCGA classification for UM is simple, accurate, and highly predictive of melanoma-related metastasis and death, more so than the AJCC classification.
癌症基因组图谱（TCGA）是美国国家癌症研究所（NCI）支持的一个综合项目，旨在探索癌症中的分子改变，包括葡萄膜黑色素瘤（UM）。这导致了 TCGA 对 UM 的分类。在本报告中，我们回顾了美国癌症联合委员会（AJCC）分类和 NCI 癌症基因组学中心（NCI CCG）基于眼球摘除标本（n = 80 只眼）和威尔斯眼医院（WEH）基于细针抽吸活检（FNAB）标本（n = 658 只眼）的 UM 的 TCGA 分类。然后，我们比较了 AJCC 与 TCGA 的准确性和可预测性。
对 AJCC 和 TCGA 分类的 UM 进行了文献回顾。评估了基于 AJCC 第 7 版和第 8 版的结果。对于 TCGA，UM 根据染色体 3 和 8 的发现进行分类，包括三体 3（D3）、单体 3（M3）、三体 8（D8）、8q 增益（8qG）或 8q 增益多个（8qGm），并分为四个类别，包括 A 类（D3/D8）、B 类（D3/8qG）、C 类（M3/8qG）和 D 类（M3/8qGm）。探讨了转移和死亡的结果，并进行了 AJCC 与 TCGA 的比较。
在 NCI CCG 研究中，有 80 只 UM 眼通过眼球摘除（n = 77）、切除（n = 2）或眶切开术（n = 1）取样，并分析发现了四个不同的遗传类别。随后在 WEH 研究中对 WEH 研究中对每个类别进行了转移和死亡结果的评估。WEH 研究回顾了 658 只通过 FNAB 取样的 UM 眼，发现 A 类（n = 342，52%）、B 类（n = 91，14%）、C 类（n = 118，18%）和 D 类（n = 107，16%）。按类别增加（A 类 vs. B 类 vs. C 类 vs. D 类）比较显示，患者年龄较大（P < 0.001）、初诊视力较差（P < 0.001）、视盘距离较远（P < 0.001）、肿瘤直径较大（P < 0.001）、肿瘤厚度较大（P < 0.001）。关于结果，更先进的 TCGA 类别显示出更高的 5 年转移风险（4% vs. 20% vs. 33% vs. 63%，P < 0.001），相应的危险比（HR）增加（1.0 vs. 4.1、10.1、30.0，P=0.01，B 类 vs. A 类和 P < 0.001，C 类 vs. A 类和 D 类 vs. A 类），以及更高的 5 年估计死亡风险（1% vs. 0% vs. 9% vs. 23%，P < 0.001），相应的 HR 增加（1 vs. 无意义 vs. 3.1 vs. 13.7，P=0.11，C 类 vs. A 类和 P < 0.001，D 类 vs. A 类）。AJCC 与 TCGA 分类的比较表明，TCGA 分类在预测 UM 的转移和死亡方面更简单、更准确、更具预测性。
UM 的 TCGA 分类简单、准确，高度预测黑色素瘤相关的转移和死亡，比 AJCC 分类更优越。
