Associate Professor; Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Anticancer Res. 2014 Mar;34(3):1227-31.
The mesenchymal-epithelial transition factor (MET) is a receptor tyrosine kinase that plays a key role in cell survival, growth, angiogenesis and metastasis. Because its expression is frequently altered in tumors, MET is currently under investigation as a potential target for anticancer therapy. The purpose of the present study was to determine the prognostic value of tumor MET expression levels in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer, in order to strengthen the rationale for targeted therapy using MET inhibitors in this breast cancer subpopulation.
We determined the expression of MET in formalin-fixed paraffin-embedded surgical specimens of ER- and HER2-positive breast cancer by immunohistochemistry.
Comparisons of MET expression with clinical parameters, including survival of the patients, were performed with MET expression as a dichotomized variable classified as high or low. Out of 78 tumors, 3 (3.8%) showed high MET expression. The analysis examining the association between MET and survival did not yield any statistically significant result regarding overall survival or disease-free survival.
ER- and HER2-positive breast carcinomas do not exhibit high MET expression. This null finding, the first to be reported in the literature, is of great importance, since it indicates that this sub-group population is not proper candidate for clinical trials with MET inhibitors.
间质-上皮转化因子(MET)是一种受体酪氨酸激酶,在细胞存活、生长、血管生成和转移中发挥关键作用。由于其在肿瘤中的表达经常发生改变,因此 MET 目前正在作为一种潜在的抗癌治疗靶点进行研究。本研究旨在确定肿瘤 MET 表达水平在雌激素受体(ER)阳性和人表皮生长因子受体 2(HER2)阳性乳腺癌患者中的预后价值,以便为在该乳腺癌亚群中使用 MET 抑制剂进行靶向治疗提供更充分的依据。
我们通过免疫组织化学法测定了 ER 和 HER2 阳性乳腺癌福尔马林固定石蜡包埋手术标本中 MET 的表达。
将 MET 表达作为高或低的二分类变量进行比较,与患者的生存等临床参数进行比较。在 78 例肿瘤中,有 3 例(3.8%)显示 MET 高表达。分析 MET 与生存之间的关系,在总生存或无病生存方面均未得出任何统计学显著结果。
ER 和 HER2 阳性乳腺癌并不表现出高 MET 表达。这一首次在文献中报道的阴性发现非常重要,因为它表明该亚组人群不适合进行 MET 抑制剂的临床试验。