Kawaguchi Y, Kono K, Mimura K, Mitsui F, Sugai H, Akaike H, Fujii H
First Department of Surgery, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi 409-3898, Japan.
Br J Cancer. 2007 Aug 20;97(4):494-501. doi: 10.1038/sj.bjc.6603885. Epub 2007 Jul 10.
We previously reported that oesophageal squamous cell carcinoma (SCC) had a relatively high incidence of EGFR and HER-2 overexpression. Thus, anti-HER family targeting may become a promising approach to treat oesophageal SCC. In the present study, we investigated (a) the distribution of EGFR and HER-2 expression in oesophageal SCC (n=66) detected by immunohistochemistry and (b) cetuximab- and/or trastuzumab-mediated biological activity (antiproliferative effect by the MTT assay, apoptosis-inducing activity by the annexin V/propidium iodide assay, and antibody-dependent cellular cytotoxicity (ADCC) by the (51)Cr-release assay) against oesophageal SCC cell lines with various levels of EGFR and HER-2. Twelve of the 66 patients (18%) showed both EGFR- and HER-2 expression. Out of both EGFR- and HER-2-positive cases, nine cases (75%) showed EGFR and HER-2 expression in individually distinct regions. Furthermore, the combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects and additional ADCC activities against not all, but several oesophageal SCC cell lines with EGFR and HER-2 expression. The combination of cetuximab and trastuzumab may be useful in the treatment of oesophageal SCC with EGFR and HER-2 expression.
我们之前报道过，食管鳞状细胞癌（SCC）中表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER-2）过表达的发生率相对较高。因此，靶向HER家族可能成为治疗食管SCC的一种有前景的方法。在本研究中，我们调查了：（a）通过免疫组织化学检测的66例食管SCC中EGFR和HER-2表达的分布情况；（b）西妥昔单抗和/或曲妥珠单抗对不同EGFR和HER-2水平的食管SCC细胞系的生物学活性（通过MTT试验检测抗增殖作用，通过膜联蛋白V/碘化丙啶试验检测凋亡诱导活性，通过51Cr释放试验检测抗体依赖性细胞毒性（ADCC））。66例患者中有12例（18%）同时显示EGFR和HER-2表达。在EGFR和HER-2均阳性的病例中，9例（75%）在各自不同区域显示EGFR和HER-2表达。此外，西妥昔单抗和曲妥珠单抗联合使用可诱导协同抗增殖作用，并对部分（而非全部）具有EGFR和HER-2表达的食管SCC细胞系产生额外的ADCC活性。西妥昔单抗和曲妥珠单抗联合使用可能对治疗具有EGFR和HER-2表达的食管SCC有用。
