Van Laere Steven, Beissbarth Tim, Van der Auwera Ilse, Van den Eynden Gert, Trinh Xuan Bich, Elst Hilde, Van Hummelen Paul, van Dam Peter, Van Marck Eric, Vermeulen Peter, Dirix Luc
Translational Cancer Research Group, Laboratory of Pathology, University of Antwerp and Oncology Center, General Hospital Sint-Augustinus, Wilrijk, Belgium.
Clin Cancer Res. 2008 Nov 15;14(22):7452-60. doi: 10.1158/1078-0432.CCR-08-1077.
We hypothesize that a gene expression profile characteristic for inflammatory breast cancer (IBC), an aggressive form of breast cancer associated with rapid cancer dissemination and poor survival, might be related to tumor aggressiveness in non-IBC (nIBC).
RNA from 17 IBC samples and 40 nIBC samples was hybridized onto Affymetrix chips. A gene signature predictive of IBC was identified and applied onto 1,157 nIBC samples with survival data of 881 nIBC samples. Samples were classified as IBC-like or nIBC-like. The IBC signature classification was compared with the classifications according to other prognostically relevant gene signatures and clinicopathologic variables. In addition, relapse-free survival (RFS) was compared by the Kaplan-Meyer method.
Classification according to the IBC signature is significantly (P < 0.05) associated with the cell-of-origin subtypes, the wound healing response, the invasive gene signature, the genomic grade index, the fibroblastic neoplasm signature, and the 70-gene prognostic signature. Significant associations (P < 0.01) were found between the IBC signature and tumor grade, estrogen receptor status, ErbB2 status, and patient age at diagnosis. Patients with an IBC-like phenotype show a significantly shorter RFS interval (P < 0.05). Oncomine analysis identified cell motility as an important concept linked with the IBC signature.
We show that nIBC carcinomas having an IBC-like phenotype have a reduced RFS interval. This suggests that IBC and nIBC show comparable phenotypic traits, for example augmented cell motility, with respect to aggressive tumor cell behavior. This observation lends credit to the use of IBC to study aggressive tumor cell behavior.
我们推测，炎性乳腺癌（IBC）——一种与癌症快速扩散及低生存率相关的侵袭性乳腺癌——的基因表达谱特征，可能与非炎性乳腺癌（nIBC）的肿瘤侵袭性有关。
将来自17个IBC样本和40个nIBC样本的RNA与Affymetrix芯片进行杂交。确定了一个预测IBC的基因特征，并将其应用于1157个nIBC样本，其中881个nIBC样本有生存数据。样本被分类为IBC样或nIBC样。将IBC特征分类与根据其他预后相关基因特征及临床病理变量的分类进行比较。此外，采用Kaplan - Meyer方法比较无复发生存率（RFS）。
根据IBC特征进行的分类与起源细胞亚型、伤口愈合反应、侵袭性基因特征、基因组分级指数、成纤维细胞瘤特征以及70基因预后特征显著相关（P < 0.05）。在IBC特征与肿瘤分级、雌激素受体状态、ErbB2状态以及诊断时患者年龄之间发现了显著相关性（P < 0.01）。具有IBC样表型的患者显示出显著更短的RFS间隔（P < 0.05）。Oncomine分析确定细胞运动性是与IBC特征相关的一个重要概念。
我们表明，具有IBC样表型的nIBC癌的RFS间隔缩短。这表明IBC和nIBC在侵袭性肿瘤细胞行为方面表现出可比的表型特征，例如增强的细胞运动性。这一观察结果支持使用IBC来研究侵袭性肿瘤细胞行为。
