Gene Expression Profiles of Estrogen Receptor-Positive and Estrogen Receptor-Negative Breast Cancers Are Detectable in Histologically Normal Breast Epithelium

被引:50
|
作者
Graham, Kelly
Ge, Xijin [4 ]
de las Morenas, Antonio [2 ]
Tripathi, Anusri [3 ]
Rosenberg, Carol L. [1 ,2 ,3 ]
机构
[1] Boston Univ, Med Ctr, Sch Med, Genet & Genom Program, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA
[3] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA
[4] S Dakota State Univ, Dept Math & Stat, Brookings, SD 57007 USA
关键词
SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; CELL-LINES; RANDOMIZED-TRIALS; ALLELE IMBALANCE; IMMUNOGLOBULIN-G; DISTINCT; TISSUE; HETEROZYGOSITY; CARCINOMAS;
D O I
10.1158/1078-0432.CCR-10-1369
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype. Experimental Design: We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases [15 estrogen receptor (ER)+, 15 ER-] we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER+), we validated selected genes using quantitative real-time PCR (qPCR). We then compared gene expression between NlEpi and invasive breast cancer using four publicly available data sets. Results: We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared with ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers (e. g., ESR1, GATA3, and CX3CL1, FABP7). qPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 25% to 53% of the genes or probes examined in four external data sets overlapped between NlEpi and the corresponding cancer subtype. Conclusions: Gene expression differs in NlEpi of breasts containing ER+ compared with ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development, and locate targets for prevention and therapy. Clin Cancer Res; 17(2); 236-46. (C)2010 AACR.
引用
收藏
页码:236 / 246
页数:11
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