Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers
Expression and mutational analysis of tyrosine kinase receptors c-kit, PDGFRα, and PDGFRβ in ovarian cancers
复制标题
DOI：
10.1016/j.humpath.2004.11.009
复制
发表时间：
2005-03-01
期刊：
影响因子：
3.3
通讯作者：
Alberts, DS
中科院分区：
文献类型：
--
作者：
Wilczynski, SP;Chen, YY;Alberts, DS
大多数患有上皮性卵巢癌的女性被诊断为晚期疾病。尽管通过手术和标准化疗减少了最初的肿瘤，但肿瘤经常复发，患者最终死于疾病。正在研究抑制酪氨酸激酶受体（TKR）的新药用于治疗，本研究旨在确定卵巢癌中3种TKR（c-kit、血小板衍生生长因子受体[PDGFR] a和PDGFR β）的表达和突变状态。用c-kit、PDGFR α和PDGFR β特异性抗体通过免疫组织化学研究了包含84个上皮性卵巢肿瘤的组织阵列。在78%的肿瘤中检测到至少一种TKR的免疫反应性。PDGFR α，.在卵巢肿瘤中表达的百分比最高（58%），而29%表达PDGFR β。研究了针对c-kit的两种商业抗体，并且33%的肿瘤用一种抗体染色，但只有6%的肿瘤用第二种抗体被解释为阳性。TKRs的激活可能通过突变发生，但通过序列分析，在6个TKRs（c-kit、PDGFR α和PDGFR β）免疫反应性升高的卵巢肿瘤中未检测到突变。酪氨酸激酶受体也可以通过其配体对受体的自分泌或旁分泌刺激而被激活。在43例（35%）同时检测c-kit受体及其配体（干细胞因子）的肿瘤中，15例同时表达这两种蛋白质，表明这种自分泌刺激反馈环可能是某些卵巢癌生长的一个因素。这项研究表明，PDGFR α，PDGFR β和c-kit在上皮性卵巢癌中表达的百分比很高，这表明酪氨酸激酶抑制剂可能有助于治疗这些肿瘤。(c)2005年爱思唯尔公司All rights reserved.
Most women with epithelial ovarian cancer are diagnosed with advanced disease. Despite surgery and initial tumor reduction by standard chemotherapy, the tumors frequently recur and the patients eventually die of their disease. New drugs that inhibit tyrosine kinase receptors (TKRs) are being investigated for treatment and this study was undertaken to determine the expression and mutational state for 3 TKRs (c-kit, platelet-derived growth factor receptor [PDGFR] a, and PDGFR beta) in ovarian cancer. Tissue arrays containing 84 epithelial ovarian tumors were studied by immunohistochemistry with antibodies specific for c-kit, PDGFR alpha, and PDGFR beta. Immunoreactivity was detected in 78% of the tumor to at least one TKR. PDGFR alpha,. was expressed in the largest percentage of ovarian tumors (58%) whereas 29% expressed PDGFR beta. Two commercial antibodies against c-kit were studied and 33% of the tumors stained with one but only 6% were interpreted as positive with the second antibody. Activation of TKRs may occur through mutations but, by sequence analysis, no mutations were detected in 6 ovarian tumors with elevated immunoreactivity for each of the TKRs (c-kit, PDGFR alpha, and PDGFR beta). Tyrosine kinase receptors could also be activated through autocrine or paracrine stimulation of receptor by its ligand. Of 43 (35%) tumors tested for both c-kit receptor and its ligand (stem cell factor), 15 expressed both proteins indicating the possibility that this autocrine stimulation feedback loop is a factor in the growth of some ovarian cancers. This study demonstrates that PDGFR alpha, PDGFR beta, and c-kit are expressed in a high percentage of epithelial ovarian cancers suggesting that tyrosine kinase inhibitors may be useful in the treatment of these tumors. (c) 2005 Elsevier Inc. All rights reserved.