Multicenter Validation of a 1,550-Gene Expression Profile for Identification of Tumor Tissue of Origin
Multicenter Validation of a 1,550-Gene Expression Profile for Identification of Tumor Tissue of Origin
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DOI：
10.1200/jco.2008.17.9762
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发表时间：
2009-05-20
影响因子：
45.3
通讯作者：
Anderson, Glenda G.
中科院分区：
文献类型：
--
作者：
Monzon, Federico A.;Lyons-Weiler, Maureen;Anderson, Glenda G.
目的：在意想不到的位置或形态学分化较差的情况下发现的基因序列可能对组织起源的确定构成重大挑战。目前的组织学和影像学技术无法在相当数量的病例中确定起源组织。本研究的目的是为了验证预先定义的1550个基因表达谱。方法4家机构采用寡核苷酸芯片技术对15种来源组织的547份冷冻标本进行处理。一半的标本是转移性肿瘤，其余的是低分化和未分化的原发性癌症，与那些作为临床挑战的癌症相似。结果在这项盲法多中心验证研究中，1550个基因表达谱在组织测定中具有很高的信息量。该研究发现总体敏感性（阳性百分比与参考诊断一致）为87.8% (95% CI， 84.7%至90.4%)，总体特异性（阴性百分比与参考诊断一致）为99.4% （95% CI， 98.3%至99.9%）。转移性肿瘤亚组（n = 258）的表现略低于低分化和未分化原发肿瘤亚组，分别为84.5%和90.7% （P = 0.04）。各实验室间差异无统计学意义。结论：本研究首次对基因表达谱进行了足够规模的、多中心的验证，以确定组织起源，仅限于低分化和未分化的原发性癌症和转移性肿瘤。这些结果表明，这应该是一个有价值的补充或替代现有的诊断方法，以评估不确定的原发性癌症。
PurposeMalignancies found in unexpected locations or with poorly differentiated morphologies can pose a significant challenge for tissue of origin determination. Current histologic and imaging techniques fail to yield definitive identification of the tissue of origin in a significant number of cases. The aim of this study was to validate a predefined 1,550-gene expression profile for this purpose.MethodsFour institutions processed 547 frozen specimens representing 15 tissues of origin using oligonucleotide microarrays. Half of the specimens were metastatic tumors, with the remainder being poorly differentiated and undifferentiated primary cancers chosen to resemble those that present as a clinical challenge.ResultsIn this blinded multicenter validation study the 1,550-gene expression profile was highly informative in tissue determination. The study found overall sensitivity ( positive percent agreement with reference diagnosis) of 87.8% (95% CI, 84.7% to 90.4%) and overall specificity ( negative percent agreement with reference diagnosis) of 99.4% ( 95% CI, 98.3% to 99.9%). Performance within the subgroup of metastatic tumors (n = 258) was found to be slightly lower than that of the poorly differentiated and undifferentiated primary tumor subgroup, 84.5% and 90.7%, respectively (P = .04). Differences between individual laboratories were not statistically significant.ConclusionThis study represents the first adequately sized, multicenter validation of a gene-expression profile for tissue of origin determination restricted to poorly differentiated and undifferentiated primary cancers and metastatic tumors. These results indicate that this profile should be a valuable addition or alternative to currently available diagnostic methods for the evaluation of uncertain primary cancers.