Identification of molecular apocrine breast tumours by microarray analysis

Identification of molecular apocrine breast tumours by microarray analysis
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DOI:
10.1038/sj.onc.1208561
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发表时间:
2005-07-01
期刊:
影响因子:
8
通讯作者:
Iggo, R
Iggo, R
中科院分区:
医学1区
文献类型:
--
作者:
Farmer, P;Bonnefoi, H;Iggo, R

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以前的乳腺癌微阵列研究确定了多个肿瘤类别,其中最突出的,命名为管腔和基底,不同的雌激素受体基因(ER)的表达。我们在这里报告的一组乳腺肿瘤的雄激素信号增加和一个'分子顶浆分泌'基因表达亲鉴定。乐来自49例可手术或局部晚期乳腺癌患者的肿瘤样本在Affytron U133 A基因表达微阵列上进行了测试。主成分分析和层次聚类将肿瘤分为三组:基底,管腔和一组我们称之为分子顶浆。所有的分子顶泌腺肿瘤有很强的顶泌腺功能的组织学检查(P = 0.0002)。分子顶浆分泌组为雄激素受体(AR)阳性,包含基底组以外的所有ER阴性肿瘤。Kolmogorov-Smirnov检验表明,雌激素信号传导在管腔组中最活跃,雄激素信号传导在分子顶浆分泌组中最活跃。ERBB 2扩增在顶浆分泌中较其他组常见。通过Wilcoxon检验鉴定最佳分裂三组的基因。平均表达的相关性。在我们的数据中,这些基因中的一部分表达为pro。在四项已发表的乳腺癌研究中,单个肿瘤的低比例表明,分子顶浆分泌肿瘤占这些研究中肿瘤的8-14%。我们的数据表明,它是可能的微阵列数据,以乳腺肿瘤细胞分为三组类固醇受体活性的基础上:管腔(ER+AR+),基础(ER+AR+)和分子顶浆(ER+AR+)。
Previous microarray studies on breast cancer identified multiple tumour classes, of which the most prominent, named luminal and basal, differ in expression of the oestrogen receptor a gene ( ER). We report here the identification of a group of breast tumours with increased androgen signalling and a 'molecular apocrine' gene expression pro. le. Tumour samples from 49 patients with large operable or locally advanced breast cancers were tested on Affymetrix U133A gene expression microarrays. Principal components analysis and hierarchical clustering split the tumours into three groups: basal, luminal and a group we call molecular apocrine. All of the molecular apocrine tumours have strong apocrine features on histological examination (P = 0.0002). The molecular apocrine group is androgen receptor (AR) positive and contains all of the ER-negative tumours outside the basal group. Kolmogorov-Smirnov testing indicates that oestrogen signalling is most active in the luminal group, and androgen signalling is most active in the molecular apocrine group. ERBB2 amplification is commoner in the molecular apocrine than the other groups. Genes that best split the three groups were identified by Wilcoxon test. Correlation of the average expression pro. le of these genes in our data with the expression pro. le of individual tumours in four published breast cancer studies suggest that molecular apocrine tumours represent 8-14% of tumours in these studies. Our data show that it is possible with microarray data to divide mammary tumour cells into three groups based on steroid receptor activity: luminal (ER+AR+), basal (ER+AR+) and molecular apocrine (ER+AR+).