Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade
Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade
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DOI：
10.1200/jco.2006.07.1522
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发表时间：
2007-04-01
影响因子：
45.3
通讯作者：
Sotiriou, Christos
中科院分区：
文献类型：
--
作者：
Loi, Sherene;Haibe-Kains, Benjamin;Sotiriou, Christos
目的许多微阵列研究报告了乳腺癌 (BC) 的不同分子特征，例如 basal 样、ErbB2 样和两到三种 luminal 样亚型。这些与不同的临床结果相关。然而，尽管基底亚型和 ErbB2 亚型被反复识别，但雌激素受体 (ER) 阳性亚型的鉴定却不一致。因此，需要对其分子定义进行细化。材料和方法我们之前报道了基因表达等级指数（GGI），它根据基因表达谱定义组织学等级。使用该算法，我们将 ER 阳性 BC 分配到高或低基因组级别亚组，并将这些亚组与之前报道的 ER 阳性分子分类进行比较。作为进一步验证，我们将 666 个 ER 阳性样本分为亚型并评估其临床结果。结果可以使用 GGI 定义两个 ER 阳性分子亚组（高基因组级别和低基因组级别）。尽管追踪单一生物途径，但这些与之前描述的管腔 A 和 B 分类高度相似，并且与使用 21 基因复发评分产生的风险组显着相关。在未经全身治疗和接受他莫昔芬治疗的人群中，这两种亚型与统计上不同的临床结果相关。结论使用基因组分级可以在多个数据集中以简单且高度可重复的方式识别两种临床上不同的 ER 阳性分子亚型。这项研究强调了增殖相关基因在预测 ER 阳性 BC 预后中的重要作用。
PurposeA number of microarray studies have reported distinct molecular profiles of breast cancers ( BC), such as basal-like, ErbB2-like, and two to three luminal-like subtypes. These were associated with different clinical outcomes. However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor ( ER) - positive subtypes has been inconsistent. Therefore, refinement of their molecular definition is needed.Materials and MethodsWe have previously reported a gene expression grade index (GGI), which defines histologic grade based on gene expression profiles. Using this algorithm, we assigned ER-positive BC to either high - or low - genomic grade subgroups and compared these with previously reported ER-positive molecular classifications. As further validation, we classified 666 ER-positive samples into subtypes and assessed their clinical outcome.ResultsTwo ER-positive molecular subgroups ( high and low genomic grade) could be defined using the GGI. Despite tracking a single biologic pathway, these were highly comparable to the previously described luminal A and B classification and significantly correlated to the risk groups produced using the 21-gene recurrence score. The two subtypes were associated with statistically distinct clinical outcome in both systemically untreated and tamoxifen-treated populations.ConclusionThe use of genomic grade can identify two clinically distinct ER-positive molecular subtypes in a simple and highly reproducible manner across multiple data sets. This study emphasizes the important role of proliferation-related genes in predicting prognosis in ER-positive BC.