Aktas Bahriye, Kasimir-Bauer Sabine, Müller Volkmar, Janni Wolfgang, Fehm Tanja, Wallwiener Diethelm, Pantel Klaus, Tewes Mitra
Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany.
Department of Gynecology and Obstetrics, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
BMC Cancer. 2016 Jul 25;16:522. doi: 10.1186/s12885-016-2587-4.
The expression of HER2, estrogen (ER) and progesterone (PR) receptor can change during the course of the disease in breast cancer (BC). Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. In this context, characterization of circulating tumor cells (CTCs) could be of relevance since metastatic tissue may be difficult to obtain for repeated analysis. Here we compared HER2/ER/PR expression profiles of primary tumors, metastases and CTCs.
Ninety-six patients with metastatic BC from seven University BC Centers in Germany were enrolled in this study. Blood was obtained at the time of first diagnosis of metastatic disease or disease progression and analyzed for CTCs using the AdnaTest BreastCancer (QIAGEN Hannover GmbH, Germany) for the expression of EpCAM, MUC-1, HER2, ER and PR. HER2 expression on CTCs was additionally assessed by immunocytochemistry using the CellSearch® assay.
The detection rate for CTCs using the AdnaTest was 43 % (36/84 patients) with the expression rates of 50 % for HER2 (18/36 patients), 19 % for ER (7/36 patients) and 8 % for PR (3/36 patients), respectively. Primary tumors and CTCs displayed a concordant HER2, ER and PR status in 59 % (p = 0.262), 39 % (p = 0.51) and 44 % (p = 0.62) of cases, respectively. For metastases and CTCs, the concordance values were 67 % for HER2 (p = 0.04), 43 % for ER (p = 0.16) and 46 % for PR (p = 0.6). Using the CellSearch® assay, the CTC-positivity rate was 53 % (42/79 patients) with HER2 expressed in 29 % (12/42) of the patients. No significant concordance (58 % and 53 %) was found when HER2 on CTCs was compared with HER2 on primary tumors (p = 0.24) and metastases (p = 0.34). Interestingly, primary tumors and metastases were highly concordant for HER2 (84 %, p = 1.13E-08), ER (90 %, p = 3.26E-10) and PR (83 %, p = 2.09E-09) and ER-and PR-positive metastases were significantly found to be of visceral origin (p = 0.03, p = 0.02).
Here we demonstrate that the molecular detection of HER2 overexpression in CTC is predictive of the HER2 status on metastases. Detailed analysis of ER and PR expression rates in tissue samples and CTCs may provide useful information for making treatment decisions.
在乳腺癌（BC）病程中，人表皮生长因子受体2（HER2）、雌激素（ER）和孕激素（PR）受体的表达可能会发生变化。因此，在疾病进展时重新评估这些标志物可能有助于优化治疗决策。在这种情况下，循环肿瘤细胞（CTC）的特征分析可能具有相关性，因为可能难以获取转移组织进行重复分析。在此，我们比较了原发性肿瘤、转移灶和CTC的HER2/ER/PR表达谱。
来自德国七个大学乳腺癌中心的96例转移性BC患者纳入本研究。在首次诊断转移性疾病或疾病进展时采集血液，使用AdnaTest BreastCancer（德国QIAGEN汉诺威有限公司）分析CTC，检测上皮细胞黏附分子（EpCAM）、黏蛋白1（MUC-1）、HER2、ER和PR的表达。此外，使用CellSearch®检测法通过免疫细胞化学评估CTC上的HER2表达。
使用AdnaTest检测CTC的检出率为43%（36/84例患者），HER2、ER和PR的表达率分别为50%（18/36例患者）、19%（7/36例患者）和8%（3/36例患者）。原发性肿瘤和CTC的HER2、ER和PR状态分别在59%（p = 0.262）、39%（p = 0.51）和44%（p = 0.62）的病例中显示一致。对于转移灶和CTC，HER2、ER和PR的一致性值分别为67%（p = 0.04）、43%（p = 0.16）和46%（p = 0.6）。使用CellSearch®检测法，CTC阳性率为53%（42/79例患者），29%（12/42）的患者表达HER2。当比较CTC上的HER2与原发性肿瘤（p = 0.24）和转移灶（p = 0.34）上的HER2时，未发现显著一致性（分别为58%和53%）。有趣的是，原发性肿瘤和转移灶在HER2（84%，p = 1.13E - 08）、ER（90%，p = 3.26E - 10）和PR（83%，p = 2.09E - 09）方面高度一致，并且ER和PR阳性的转移灶显著发现源自内脏（p = 0.03，p = 0.02）。
在此我们证明，CTC中HER2过表达的分子检测可预测转移灶上的HER2状态。对组织样本和CTC中ER和PR表达率的详细分析可能为制定治疗决策提供有用信息。
