Washington University and Siteman Cancer Center, St. Louis, Missouri, USA.
Ophthalmology. 2012 Aug;119(8):1596-603. doi: 10.1016/j.ophtha.2012.02.017. Epub 2012 Apr 21.
This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk).
Prospective, multicenter study.
A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.
Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status.
Patients were managed for their primary tumor and monitored for metastasis.
The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status.
The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.
本研究评估了一种 15 基因表达谱（GEP）检测的预后性能，该检测将原发性眼后葡萄膜黑色素瘤分为预后亚组：1 类（低转移风险）和 2 类（高转移风险）。
前瞻性、多中心研究。
共招募了 12 个独立中心的 459 例眼后葡萄膜黑色素瘤患者。
肿瘤通过 GEP 分类为 1 类或 2 类。前 260 个样本还使用单核苷酸多态性检测分析了染色体 3 状态。净重新分类改善分析用于比较 GEP 与第 7 版临床肿瘤-淋巴结-转移（TNM）分类和染色体 3 状态的预后准确性。
对患者的原发性肿瘤进行管理并监测转移情况。
GEP 检测成功分类了 459 例中的 446 例（97.2%）。276 例（61.9%）为 1 类，170 例（38.1%）为 2 类。中位随访时间为 17.4 个月（平均 18.0 个月）。3 例 1 类病例（1.1%）和 44 例 2 类病例（25.9%）中检测到转移（对数秩检验，P<10(-14)）。尽管 GEP 2 类与单体 3 之间存在关联（Fisher 确切检验，P<0.0001），但在 260 个肿瘤中有 54 个（20.8%）在 GEP 和染色体 3 状态上存在不一致，其中 GEP 显示出更好的预后准确性（对数秩检验，P=0.0001）。通过多变量 Cox 建模，GEP 类与转移的独立相关性强于任何其他预后因素（P<0.0001）。染色体 3 状态未提供与 GEP 无关的独立预后信息（P=0.2）。在 3 年随访时，GEP 对 TNM 分类的净重新分类改善率为 0.43（P=0.001），对染色体 3 状态的净重新分类改善率为 0.38（P=0.004）。
GEP 检测的技术成功率很高，是所有分析因素中最准确的预后标志物。GEP 提供了比临床 TNM 分类和染色体 3 状态更显著的预后准确性提高。染色体 3 状态未提供与 GEP 无关的预后信息。
