Bendrat Klaus, Fritz Peter, Müller Simon, Brockmöller Sylvia, Debus Annegret, Friedrichs Kay, Lindner Christoph, Brinkmann Friedhelm, Heidemann Else, Niendorf Axel
Institute for Molecular Cell Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany Pathology Hamburg-West, Hamburg, Germany.
Oncological Center Stuttgart e.V., Stuttgart, Germany Institute for Pathology, Robert Bosch Hospital Stuttgart, Stuttgart, Germany.
Anticancer Res. 2016 Aug;36(8):3855-63.
The receptors for estrogen (ESR1) and progesterone (PGR) are both part of the same signaling pathway and routinely used for breast cancer stratification. We tested the hypothesis if a coordinated analysis could add extra information for prognostic stratification.
ESR1 and PGR gene expression was first investigated by quantitative reverse transcription polymerase chain reaction in fresh-frozen invasive ductal breast cancer samples (Hamburg collective, case-control, n=317). Our results were then tested using two datasets generated by different technical approaches: i) a public DNA-chip data set (GSE3494, n=251) and ii) semiquantitative protein expression data based on immunohistochemistry (Stuttgart collective, n=18,528).
The PGR/ESR1 gene-expression ratio was a prognostic indicator in those with ESR1/PGR-positive breast cancer (Hamburg collective), with a high PGR/ESR1 expression ratio indicating a favorable outcome. In all three collectives, the PGR/ESR1 mRNA ratio or its protein equivalent was a univariate prognostic factor and also a multivariate prognostic factor in the Hamburg and Stuttgart collectives.
Calculation of the PGR/ESR1 gene-expression ratio and its immunohistochemical surrogate could be a useful and simple addition to routine breast cancer diagnostics. A high PGR/ESR1 ratio could be indicative of a favorable clinical outcome.
雌激素受体（ESR1）和孕激素受体（PGR）均属于同一信号通路的一部分，常用于乳腺癌分层。我们检验了这样一个假设，即协同分析是否可为预后分层增添额外信息。
首先通过定量逆转录聚合酶链反应对新鲜冷冻的浸润性导管癌样本（汉堡队列，病例对照，n = 317）中的ESR1和PGR基因表达进行研究。然后使用通过不同技术方法生成的两个数据集对我们的结果进行检验：i）一个公开的DNA芯片数据集（GSE3494，n = 251）和ii）基于免疫组织化学的半定量蛋白表达数据（斯图加特队列，n = 18,528）。
在ESR1/PGR阳性乳腺癌患者（汉堡队列）中，PGR/ESR1基因表达比值是一个预后指标，PGR/ESR1表达比值高表明预后良好。在所有三个队列中，PGR/ESR1 mRNA比值或其蛋白等效物是一个单因素预后因素，在汉堡和斯图加特队列中也是一个多因素预后因素。
计算PGR/ESR1基因表达比值及其免疫组化替代指标可能是常规乳腺癌诊断中一种有用且简便的补充方法。高PGR/ESR1比值可能预示着良好的临床结局。
