Department of Medical Oncology, Chinese Academy of Medical Sciences, Beijing, China.
Chin Med J (Engl). 2012 Nov;125(22):4104-10.
Measurement of human epidermal growth factor receptor 2 (HER2) protein in the serum of metastatic breast cancer patients has previously been reported, but there are no consistent data to support the clinical utility of serum HER2 extracellular domain for patients with early stage breast cancer. We aimed to evaluate the correlation between serum extracellular domain levels and tissue HER2 expression, and analyzed their relationship with clinico-pathological parameters in patients with early stage disease.
A prospective study was conducted on 232 breast cancer patients with stage I-III prior to treatment. Preoperative serum samples were measured by enzyme-linked immunosorbent assay. Tissue HER2 status was analyzed by immunohistochemistry and fluorescence in situ hybridization assays.
The median serum extracellular domain concentration was 6.8 ng/ml. The best diagnostic cut-off value was 7.4 ng/ml, with 62.9% sensitivity and 85.3% specificity. High serum extracellular domain levels were reported in 89 patients (38.3%), and HER2-positive expression was observed in 77 patients (33.2%). Multivariate analysis showed that elevated serum extracellular domain correlated with postmenopausal status (P < 0.001), high histological grade (P < 0.001), negativity of both estrogen (P = 0.012) and progesterone receptors (P < 0.001), and high levels of carcinoembryonic antigen 153 (P = 0.048).
We recommend that 7.4 ng/ml should be used as the cut-off value when evaluating serum extracellular domain levels in early stage of breast cancer. Patients with high serum extracellular domain levels have a certain clinico-pathological characteristics, may provide a basis for clinical practice.
先前已有转移性乳腺癌患者血清人表皮生长因子受体 2（HER2）蛋白检测的报道，但尚无一致数据支持早期乳腺癌患者血清 HER2 细胞外域用于临床的实用性。本研究旨在评估血清细胞外域水平与组织 HER2 表达之间的相关性，并分析其与早期疾病患者临床病理参数的关系。
对 232 例 I-III 期乳腺癌患者进行了一项前瞻性研究，在治疗前采集了术前血清样本，采用酶联免疫吸附试验进行检测。采用免疫组织化学和荧光原位杂交技术分析组织 HER2 状态。
血清细胞外域浓度的中位数为 6.8ng/ml。最佳诊断截断值为 7.4ng/ml，其敏感性为 62.9%，特异性为 85.3%。89 例（38.3%）患者血清细胞外域水平升高，77 例（33.2%）患者 HER2 阳性表达。多变量分析显示，血清细胞外域水平升高与绝经后状态（P<0.001）、高组织学分级（P<0.001）、雌激素（P=0.012）和孕激素受体（P<0.001）阴性以及癌胚抗原 153 水平升高（P=0.048）相关。
建议将 7.4ng/ml 作为评估早期乳腺癌患者血清细胞外域水平的截断值。血清细胞外域水平较高的患者具有一定的临床病理特征，可能为临床实践提供依据。
