OSI Pharmaceuticals LLC, 2860 Wilderness Place, Boulder, CO 80301, USA.
Anticancer Res. 2012 Feb;32(2):537-52.
E-Cadherin and vimentin protein expression was assessed in late stage non-small cell lung cancer tumors from the placebo controlled clinical trial, NCIC-CTG BR.21, to determine if these markers had the potential to predict outcome of erlotinib therapy. E-Cadherin and vimentin protein expression levels were assessed in tumors from 95 patients, who were representative of the overall population, using semi-quantitative immunohistochemistry. The percentage of tumor cells with grades 0, 1, 2, or 3 membrane staining of E-cadherin and cytoplasmic staining of vimentin was measured. Three scoring methods and multiple cut-offs were explored to determine if these markers were able to divide patients into groups with different overall survival (OS). A cut-off point for E-cadherin of ≥40% tumor cells with staining of +2 and +3 and a cut-off for vimentin of ≥10% of tumors cell with any staining provided the optimal stratification. The OS hazard ratio (HR) for E-cadherin(+) versus E-cadherin(-) in the erlotinib-treated patients was 0.68 (0.35-1.33) compared with 1.48 (0.69-3.15) in the placebo patients and the OS (HR) for erlotinib versus placebo was 0.47 (0.26-0.88) in E-cadherin(+) patients compared with 1.12 (0.52-2.44) in the E-cadherin(-) patients. The OS (HR) for vimentin(+) versus vimentin(-) in the erlotinib-treated patients was 0.65 (0.31-1.38) compared to 2.32 (1.09-4.94) in the placebo-treated patients and the OS (HR) for erlotinib versus placebo was 0.26 (0.11-0.63) in vimentin(+) compared to 0.99 (0.55-1.76) in the vimentin(-) patients. Similar trends were observed for progression-free survival and response rate. E-Cadherin and vimentin are biomarkers worthy of additional study as predictive markers of outcome of erlotinib therapy.
E-钙黏蛋白和波形蛋白蛋白表达在非小细胞肺癌 NCIC-CTG BR.21 临床试验的安慰剂对照期进行评估，以确定这些标志物是否有可能预测厄洛替尼治疗的结果。使用半定量免疫组化方法评估了 95 例患者肿瘤中的 E-钙黏蛋白和波形蛋白的蛋白表达水平，这些患者代表了总体人群。测量了具有 0、1、2 或 3 级膜染色 E-钙黏蛋白和细胞质染色波形蛋白的肿瘤细胞的百分比。探索了三种评分方法和多个截止值，以确定这些标志物是否能够将患者分为具有不同总生存期 (OS) 的组。E-钙黏蛋白的截止值≥40%肿瘤细胞染色为+2 和+3，波形蛋白的截止值≥10%肿瘤细胞有任何染色，这提供了最佳分层。与安慰剂组相比，厄洛替尼治疗患者中 E-钙黏蛋白(+)与 E-钙黏蛋白(-)的 OS 风险比 (HR) 为 0.68(0.35-1.33)，而安慰剂组为 1.48(0.69-3.15)，E-钙黏蛋白(+)患者中厄洛替尼与安慰剂的 OS(HR)为 0.47(0.26-0.88)，而 E-钙黏蛋白(-)患者为 1.12(0.52-2.44)。与安慰剂组相比，厄洛替尼治疗患者中波形蛋白(+)与波形蛋白(-)的 OS 风险比 (HR) 为 0.65(0.31-1.38)，而安慰剂组为 2.32(1.09-4.94)，E-钙黏蛋白(+)患者中厄洛替尼与安慰剂的 OS(HR)为 0.26(0.11-0.63)，而波形蛋白(-)患者为 0.99(0.55-1.76)。无进展生存期和反应率也观察到类似的趋势。E-钙黏蛋白和波形蛋白是作为厄洛替尼治疗结果预测标志物的有价值的生物标志物，值得进一步研究。
