Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.

Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.
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DOI:
10.1016/j.ophtha.2012.02.017
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发表时间:
2012-08
期刊:
影响因子:
13.7
通讯作者:
Harbour JW
Harbour JW
中科院分区:
医学1区
文献类型:
--
作者:
Onken MD;Worley LA;Char DH;Augsburger JJ;Correa ZM;Nudleman E;Aaberg TM Jr;Altaweel MM;Bardenstein DS;Finger PT;Gallie BL;Harocopos GJ;Hovland PG;McGowan HD;Milman T;Mruthyunjaya P;Simpson ER;Smith ME;Wilson DJ;Wirostko WJ;Harbour JW

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这项研究评估了15个基因表达谱(GEP)测定的预后表现,将原发性葡萄膜后黑色素瘤划分为预后亚组:1级(低转移风险)和2级(高转移风险)。前瞻性、多中心研究。来自12个独立中心的459例葡萄膜后黑色素瘤患者入组。GEP将肿瘤分为1级和2级。用单核苷酸多态性测定法分析了前260个样本的3号染色体状态。进行净重分类改进分析,比较GEP与第7版临床肿瘤-淋巴结-转移(TNM)分类和3号染色体状态的预后准确性。对患者的原发肿瘤进行治疗,并监测转移情况。GEP试验成功分类446/459例(97.2%)。GEP为1级276例(61.9%),2级170例(38.1%)。中位随访时间为17.4个月(平均18.0个月)。1级3例(1.1%)、2级44例(25.9%)存在转移(log rank检验,P<10−14)。虽然GEP 2级与3号单体存在相关性(Fisher精确检验,P<0.0001),但54/260例(20.8%)肿瘤的GEP与3号染色体状态不一致,其中GEP表现出更高的预后准确性(log rank检验,P=0.0001)。通过多变量Cox模型,与其他预后因素相比,GEP分级与转移的独立相关性更强(P<0.0001)。3号染色体状态不提供与GEP无关的其他预后信息(P=0.2)。在三年的随访中,GEP比TNM分类的净重分类改善为0.43 (P=0.001),比3号染色体状态的净重分类改善为0.38 (P=0.004)。GEP试验具有很高的技术成功率,是所有分析因素中最准确的预后标志物。与临床TNM分类和3号染色体状态相比,GEP在预后准确性方面提供了非常显著的改善。3号染色体状态不能提供与GEP无关的预后信息。
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. 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 to the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and to chromosome 3 status. Patients were managed for their primary tumor and monitored for metastasis. The GEP assay successfully classified 446/459 (97.2%) cases. 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 (1.1%) class 1 cases and 44 (25.9%) class 2 cases (log rank test, P<10−14). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54/260 (20.8%) tumors were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log rank test, P=0.0001). 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 three 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. 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.
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