ESR1 扩增在乳腺癌中罕见，与高分级和高增殖相关：一项多重连接依赖探针扩增研究。
ESR1 amplification is rare in breast cancer and is associated with high grade and high proliferation: a multiplex ligation-dependent probe amplification study.
机构信息
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
出版信息
Anal Cell Pathol (Amst). 2010;33(1):13-8. doi: 10.3233/ACP-CLO-2010-0527.
BACKGROUND
Expression of estrogen receptor alpha (ERα) is predictive for endocrine therapy response and an important prognostic factor in breast cancer. Overexpression of ERα can be caused by estrogen receptor 1 (ESR1) gene amplification and was originally reported to be a frequent event associated with a significantly longer survival for ER-positive women treated with adjuvant tamoxifen monotherapy, which was however questioned by subsequent studies.
METHODS
This study aimed to reanalyze the frequency of ESR1 amplification by multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH), and to assess clinicopathologic correlations. MLPA was performed in a group of 135 breast cancer patients, and gains/amplifications were subjected to FISH.
RESULTS
True ESR1 amplification by MLPA was rare (2%) and only 6% more patients showed a modest gain of ESR1. All MLPA-detected ESR1 amplifications and nearly all ESR1 gains were also FISH amplified and gained, but not all FISH amplifications/gains were MLPA amplified/gained, leading to an overall concordance of only 60% between both techniques. All 3 MLPA and FISH ESR1 amplified cases had high ERα expression, but there was no obvious correlation between ESR1 gain and ER status by IHC. ESR1 gains/amplifications were not associated with HER2 gain/amplification, but seemed to be associated with older age. Surprisingly, ESR1 gain/amplification was not associated with low grade as reported previously, but correlated with high grade and high proliferation. Furthermore, ESR1 gain/amplification by MLPA was not associated with nodal status or tumor size (pT status).
CONCLUSIONS
ESR1 amplification as detected by MLPA is rare in breast cancer, and seems to be associated with high ERα expression, high age, high grade and high proliferation. This study confirms previous studies that showed differences in the ESR1 amplification frequencies detected by different techniques.
背景
雌激素受体 alpha（ERα）的表达可预测内分泌治疗反应，是乳腺癌的重要预后因素。雌激素受体 1（ESR1）基因扩增可导致 ERα 过表达，最初报道称，在接受辅助他莫昔芬单药治疗的 ER 阳性女性中，这种情况与显著延长生存时间有关，但随后的研究对此提出了质疑。
方法
本研究旨在通过多重连接依赖性探针扩增（MLPA）和荧光原位杂交（FISH）重新分析 ESR1 扩增的频率，并评估临床病理相关性。对一组 135 例乳腺癌患者进行 MLPA 检测，对获得/扩增的基因进行 FISH 检测。
结果
通过 MLPA 检测到的真正 ESR1 扩增很少（2%），只有 6%的患者出现 ESR1 适度获得。所有 MLPA 检测到的 ESR1 扩增和几乎所有的 ESR1 获得均经 FISH 扩增和获得，但并非所有的 FISH 扩增/获得都可被 MLPA 扩增/获得，因此两种技术的总体一致性仅为 60%。所有 3 例 MLPA 和 FISH ESR1 扩增病例均表现出高 ERα 表达，但 ESR1 获得与 IHC 检测的 ER 状态之间没有明显相关性。ESR1 获得/扩增与 HER2 获得/扩增无关，但似乎与年龄较大有关。令人惊讶的是，ESR1 获得/扩增与先前报道的低级别无关，而是与高级别和高增殖相关。此外，MLPA 检测到的 ESR1 获得/扩增与淋巴结状态或肿瘤大小（pT 状态）无关。
结论
通过 MLPA 检测到的 ESR1 扩增在乳腺癌中很少见，并且似乎与高 ERα 表达、高龄、高级别和高增殖相关。本研究证实了之前的研究，即不同技术检测到的 ESR1 扩增频率存在差异。
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