Prospective Gene Signature Study Using microRNA to Identify the Tissue of Origin in Patients with Carcinoma of Unknown Primary
Prospective Gene Signature Study Using microRNA to Identify the Tissue of Origin in Patients with Carcinoma of Unknown Primary
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DOI：
10.1158/1078-0432.ccr-10-2599
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发表时间：
2011-06-15
影响因子：
11.5
通讯作者：
Raber, Martin N.
中科院分区：
文献类型：
--
作者：
Varadhachary, Gauri R.;Spector, Yael;Raber, Martin N.
目的：准确识别原发性未知癌（CUP）患者的组织来源（ToO）可能有助于为假定的原发性癌症定制治疗，从而改善临床结局。我们前瞻性地研究了基于microRNA的检测的性能，以确定在CUP patients.Experimental Design的ToO：福尔马林固定石蜡包埋（FFPE）转移组织从104例患者进行了审查，其中87个包含足够的肿瘤进行测试。该分析定量48种microRNA，并通过使用生物学动机的二叉决策树和K-最近邻（KNN）分配25种肿瘤诊断之一。分析预测进行了比较，与临床病理特征，并在适当的情况下，治疗responsibility.Results：74的87例成功处理。在84%成功处理的病例中（占所有尝试样本的71%），检测结果与临床病理特征一致或相容。在65例患者中，病理学和免疫组化（IHC）提示诊断或（更常见）鉴别诊断。其中，55例（85%）病例的分析与临床病理表现一致或相容。在9例非贡献性IHC患者中，该检测提供了ToO预测，该预测与7 cases.Conclusions的临床表现相一致：在这项前瞻性研究中，microRNA诊断与大多数病例的临床病理学表现相一致。在适当的CUP子集中进行比较有效性研究试验，以评估分子谱分析的额外益处。microRNA分析可能对那些转移的IHC谱不能诊断或留下大量鉴别诊断的患者特别有用。Clin Cancer Res; 17（12）; 4063-70. (C)2011年AACR。
Purpose: Accurate identification of tissue of origin (ToO) for patients with carcinoma of unknown primary (CUP) may help customize therapy to the putative primary and thereby improve the clinical outcome. We prospectively studied the performance of a microRNA-based assay to identify the ToO in CUP patients.Experimental Design: Formalin-fixed paraffin-embedded (FFPE) metastatic tissue from 104 patients was reviewed and 87 of these contained sufficient tumor for testing. The assay quantitates 48 microRNAs and assigns one of 25 tumor diagnoses by using a biologically motivated binary decision tree and a K-nearest neighbors (KNN). The assay predictions were compared with clinicopathologic features and, where suitable, to therapeutic response.Results: Seventy-four of the 87 cases were processed successfully. The assay result was consistent or compatible with the clinicopathologic features in 84% of cases processed successfully (71% of all samples attempted). In 65 patients, pathology and immunohistochemistry (IHC) suggested a diagnosis or (more often) a differential diagnosis. Out of those, the assay was consistent or compatible with the clinicopathologic presentation in 55 (85%) cases. Of the 9 patients with noncontributory IHC, the assay provided a ToO prediction that was compatible with the clinical presentation in 7 cases.Conclusions: In this prospective study, the microRNA diagnosis was compatible with the clinicopathologic picture in the majority of cases. Comparative effectiveness research trials evaluating the added benefit of molecular profiling in appropriate CUP subsets are warranted. MicroRNA profiling may be particularly helpful in patients in whom the IHC profile of the metastasis is nondiagnostic or leaves a large differential diagnosis. Clin Cancer Res; 17(12); 4063-70. (C) 2011 AACR.