Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10-Magnuson CC, Room 2A10, 10 Center Drive, Bethesda, MD 20892, USA.
J Neurooncol. 2011 Jan;101(2):199-206. doi: 10.1007/s11060-010-0250-5. Epub 2010 Jul 10.
Chordomas are low to intermediate grade malignancies that arise from remnants of embryonic notochord. They often recur after surgery and are highly resistant to conventional adjuvant therapies. Recently, the development of effective targeted molecular therapy has been investigated in chordomas that show receptors for tyrosine kinase (RTKs) activation. Expression of specific RTKs such as Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial transition factor (c-MET) in chordomas may offer valuable therapeutic options. We investigated changes in copy number of chromosome 7 and correlated it with EGFR gene status and EGFR and c-MET protein expression in 22 chordoma samples. Chromosome 7 copy number was evaluated by chromogenic in situ hybridization (CISH) and protein expression of EGFR and c-MET by immunohistochemistry. Tumors mostly showed conventional histopathologic features and were found mainly in sacral (41%) and cranial sites (54.5%). Aneusomy of chromosome 7 was seen in 73% of the samples, 62% of primary tumors and in all recurrent chordomas. EGFR and c-MET were both expressed, but only c-MET protein expression was significantly correlated with chromosome 7 aneusomy (P ≤ 0.001). c-MET overexpression may represent an early chromosome 7 alteration that could play an important role during chordoma pathogenesis. c-MET overexpression shows promise as a molecular marker of response to targeted molecular therapy in the treatment of chordomas.
脊索瘤是一种低度到中度恶性肿瘤，来源于胚胎脊索的残余组织。它们在手术后常常复发，对常规辅助治疗具有高度耐药性。最近，在表现出酪氨酸激酶（RTKs）激活受体的脊索瘤中，已经研究了有效的靶向分子治疗的发展。脊索瘤中特定 RTKs（如表皮生长因子受体 [EGFR] 和间充质-上皮转化因子 [c-MET]）的表达可能提供有价值的治疗选择。我们研究了 22 例脊索瘤样本中染色体 7 拷贝数的变化，并将其与 EGFR 基因状态以及 EGFR 和 c-MET 蛋白表达相关联。通过显色原位杂交（CISH）评估染色体 7 的拷贝数，通过免疫组织化学评估 EGFR 和 c-MET 的蛋白表达。肿瘤主要表现为常规组织病理学特征，主要位于骶骨（41%）和颅部（54.5%）。73%的样本存在染色体 7 非整倍性，62%的原发性肿瘤和所有复发性脊索瘤均存在染色体 7 非整倍性。EGFR 和 c-MET 均有表达，但只有 c-MET 蛋白表达与染色体 7 非整倍性显著相关（P ≤ 0.001）。c-MET 过表达可能代表染色体 7 改变的早期事件，在脊索瘤发病机制中可能发挥重要作用。c-MET 过表达有望成为脊索瘤靶向分子治疗反应的分子标志物。
