Holst Frederik, Stahl Phillip R, Ruiz Christian, Hellwinkel Olaf, Jehan Zeenath, Wendland Marc, Lebeau Annette, Terracciano Luigi, Al-Kuraya Khawla, Jänicke Fritz, Sauter Guido, Simon Ronald
Department of Pathology, University Medical Center Hamburg Eppendorf, D-20246 Hamburg, Germany.
Nat Genet. 2007 May;39(5):655-60. doi: 10.1038/ng2006. Epub 2007 Apr 8.
Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers.
我们使用Affymetrix 10K SNP基因芯片筛选乳腺癌中的基因拷贝数变化，在6q25处检测到编码雌激素受体α的ESR1基因的单基因扩增。随后对2000多个临床乳腺癌样本进行的组织芯片分析显示，20.6%的乳腺癌存在ESR1扩增。与无ESR1扩增的癌症患者中66.6%的比例相比，99%的ESR1扩增肿瘤显示雌激素受体蛋白过表达（P<0.0001）。在175名接受辅助他莫昔芬单药治疗的女性中，ESR1扩增的癌症患者的生存期明显长于无ESR1扩增的雌激素受体表达阳性癌症患者（P = 0.023）。值得注意的是，我们还在乳腺良性和癌前疾病中发现了ESR1扩增，这表明ESR1扩增可能是乳腺增生性疾病中的常见机制，也是大部分乳腺癌中非常早期的基因改变。
