表皮-间质转化在 EGFR-TKI 获得性耐药肺腺癌中的作用。
Epithelial-mesenchymal transition in EGFR-TKI acquired resistant lung adenocarcinoma.
机构信息
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
出版信息
Anticancer Res. 2010 Jul;30(7):2513-7.
BACKGROUND
The epithelial to mesenchymal transition (EMT) may well play a part in determining the sensitivity to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). However to date, no study has investigated the association between the EMT status and acquired resistance using cancer specimens.
PATIENTS AND METHODS
Immunohistochemical (IHC) staining was used to analyse the protein expression of epithelial and mesenchymal markers in tumour samples from lung adenocarcinoma patients. Mutations in the EGFR and K-ras gene were also examined.
RESULTS
All patients showed a positive expression of epithelial markers in sensitive tumours. Tumour in 4 (44.4%) out of 9 patients showed down-regulation of epithelial markers or up-regulation of mesenchymal markers. The change in the EMT status between pre-and post-treatment was shown in 2 cases each with and without the T790M mutation.
CONCLUSION
EMT plays a role in approximately half of the cases of resistance to EGFR-TKI, independent of T790M mutation.
背景
上皮间质转化（EMT）很可能在决定表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）的敏感性方面发挥作用。然而，迄今为止，尚无研究使用癌症标本探讨 EMT 状态与获得性耐药之间的关系。
患者与方法
采用免疫组织化学（IHC）染色法分析肺腺癌患者肿瘤样本中上皮和间充质标志物的蛋白表达。同时还检测了 EGFR 和 K-ras 基因突变。
结果
所有患者的敏感肿瘤均呈上皮标志物阳性表达。9 例患者中有 4 例（44.4%）的肿瘤表现为上皮标志物下调或间充质标志物上调。在有和没有 T790M 突变的 2 例患者中，均显示出 EMT 状态在治疗前后的变化。
结论
EMT 在大约一半的 EGFR-TKI 耐药病例中发挥作用，与 T790M 突变无关。
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