A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile.
A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile.
复制标题
DOI：
10.1007/978-1-62703-727-3_22
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Harbour, J William
中科院分区：
文献类型：
--
作者：
Harbour, J William
葡萄膜（眼部）黑色素瘤是一种侵袭性癌症，在多达一半的患者中发生转移。葡萄膜黑色素瘤优先扩散到肝脏，并且转移性疾病几乎总是致命的。对于晚期转移性疾病没有有效的治疗方法，因此提高生存率的最有希望的策略是在早期检测转移或在辅助环境中治疗高危患者。一个准确的测试，以确定高风险的患者将允许这样的个性化管理，以及分层的高风险患者的辅助治疗的临床试验。我们开发了一种基因表达谱（GEP），用于区分具有低转移风险（1类肿瘤）和具有高转移风险（2类肿瘤）的原发性葡萄膜黑色素瘤。我们将GEP从高密度微阵列平台迁移到基于15个基因的qPCR检测，该检测现在在美国病理学家学院（CAP）认可的临床实验室改进修正案（CLIA）认证的实验室中进行，该实验室在常规临床基础上对通过细针抽吸获得的非常小的样本和福尔马林固定的存档标本进行检测。我们与多个中心合作，证明我们的样本采集方案易于学习和执行，并且可以安全可靠地从遥远的地方运输样本，故障率非常低。最后，我们在一项多中心前瞻性研究中表明，我们的GEP检测在预测哪些患者将发生转移性疾病方面具有高度准确性，并且显著上级以前的金标准，即3号染色体检测3号单体。这是葡萄膜黑色素瘤中唯一经过如此广泛验证的预后测试，目前正在美国和加拿大的100多个中心以商品名DecisionDx-UM的商业形式使用。
Uveal (ocular) melanoma is an aggressive cancer that metastasizes in up to half of patients. Uveal melanoma spreads preferentially to the liver, and the metastatic disease is almost always fatal. There are no effective therapies for advanced metastatic disease, so the most promising strategy for improving survival is to detect metastasis at an earlier stage or to treat high-risk patients in an adjuvant setting. An accurate test for identifying high-risk patients would allow for such personalized management as well as for stratification of high-risk patients into clinical trials of adjuvant therapy. We developed a gene expression profile (GEP) that distinguishes between primary uveal melanomas that have a low metastatic risk (class 1 tumors) and those with a high metastatic risk (class 2 tumors). We migrated the GEP from a high-density microarray platform to a 15-gene, qPCR-based assay that is now performed in a College of American Pathologists (CAP)-accredited Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory on a routine clinical basis on very small samples obtained by fine needle aspiration and on archival formalin-fixed specimens. We collaborated with several centers to show that our specimen collection protocol was easily learned and performed and that it allowed samples to be safely and reliably transported from distant locations with a very low failure rate. Finally, we showed in a multicenter, prospective study that our GEP assay is highly accurate for predicting which patients will develop metastatic disease, and it was significantly superior to the previous gold standard, chromosome 3 testing for monosomy 3. This is the only prognostic test in uveal melanoma ever to undergo such extensive validation, and it is currently being used in a commercial format under the trade name DecisionDx-UM in over 100 centers in the USA and Canada.