Kong Sun-Young, Nam Byung-Ho, Lee Keun Seok, Kwon Youngmee, Lee Eun Sook, Seong Moon-Woo, Lee Do Hoon, Ro Jungsil
Research Institute & Hospital, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
Clin Chem. 2006 Aug;52(8):1510-5. doi: 10.1373/clinchem.2006.067512. Epub 2006 Jun 15.
Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) are reliable ways to identify overexpression or amplification of the HER-2/neu (HER2, symbol ERBB2) gene, but each technique requires a high-quality tissue sample, which may not be available. We investigated whether serum concentrations of the HER2 extracellular domain (ECD) can be used as an alternative to tissue HER2 status in metastatic breast cancer, and we defined an optimal decision-level concentration of serum HER2 for prediction of tissue HER2 status.
In 195 patients with metastatic breast cancer, we determined HER2 expression by IHC and performed FISH analysis on tumors for which IHC staining was graded as 2+. We measured serum HER2 by immunoassay and used ROC curve analysis to determine optimal serum HER2 ECD concentrations for differentiation between positive and negative HER2 status.
IHC results were 0/1+ for 30 (15%) of the patients, 2+ for 89 (46%), and 3+ for 76 (39%). FISH revealed HER2 amplification in 19 (21%) of the IHC 2+ tumors. Mean (SE) serum HER2 ECD was 22.2 (5.1) microg/L in the tissue HER2-negative group, significantly lower than the concentration of 363 (96) microg/L in the tissue HER2-positive group (P<0.0001). ROC curve analysis showed 95% specificity and 62% sensitivity for tissue HER2 positivity at 37 microg/L of serum HER2.
To use serum HER2 concentration as an alternative to direct determination of tissue HER2 status, we suggest 37 microg/L as a cutoff for predicting positive tissue HER2 with 95% specificity. Sensitivity, however, is low.
免疫组织化学（IHC）和荧光原位杂交（FISH）是鉴定HER-2/neu（HER2，符号ERBB2）基因过表达或扩增的可靠方法，但每种技术都需要高质量的组织样本，而这可能无法获取。我们研究了HER2细胞外结构域（ECD）的血清浓度是否可作为转移性乳腺癌组织HER2状态的替代指标，并确定了用于预测组织HER2状态的血清HER2最佳判定浓度。
在195例转移性乳腺癌患者中，我们通过IHC确定HER2表达，并对IHC染色评分为2+的肿瘤进行FISH分析。我们通过免疫测定法测量血清HER2，并使用ROC曲线分析来确定区分HER2阳性和阴性状态的最佳血清HER2 ECD浓度。
30例（15%）患者的IHC结果为0/1+，89例（46%）为2+，76例（39%）为3+。FISH显示，在IHC 2+的肿瘤中，19例（21%）存在HER2扩增。组织HER2阴性组的血清HER2 ECD平均（SE）为22.2（5.1）μg/L，显著低于组织HER2阳性组的363（96）μg/L（P<0.0001）。ROC曲线分析显示，血清HER2为37μg/L时，组织HER2阳性的特异性为95%，敏感性为62%。
为了将血清HER2浓度用作直接测定组织HER2状态的替代方法，我们建议将37μg/L作为预测组织HER2阳性的临界值，特异性为95%。然而，敏感性较低。
