Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome
Tyrosine kinase receptor expression in chordomas: phosphorylated AKT correlates inversely with outcome
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DOI：
10.1016/j.humpath.2012.11.024
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发表时间：
2013-09-01
期刊：
影响因子：
3.3
通讯作者：
Begnami, Maria Dirlei
中科院分区：
文献类型：
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作者：
de Castro, Carolina Vieira;Guimaraes, Gustavo;Begnami, Maria Dirlei
脊索瘤是一种罕见的肿瘤，起源于脊索残余。酪氨酸激酶受体（RTK）在这些病变中改变。我们使用包含58个脊索瘤的组织微阵列，通过免疫组织化学和荧光原位杂交检测血小板衍生生长因子受体（PDGFR）-α和PDGFR-β、表皮生长因子受体（EGFR）、c-Met、c-Kit、pAKT、哺乳动物雷帕霉素靶蛋白和HER 2的表达。免疫组织化学显示，大多数肿瘤对PDGFR-α（92%）、PDGFR-β（85%）、c-Kit（77.4%）、c-Met（96%）、pAKT（82%）、哺乳动物雷帕霉素靶标（56%）、HER 2（24%）和EGFR（26%）呈阳性。在13例可用于荧光原位杂交分析的病例中，无法确定HER 2或EGFR的扩增或缺失;然而，在29%的病例中检测到7号染色体多体性。与较差生存率直接相关的唯一因素是pAKT阳性（P = 0.042）。pAKT阴性脊索瘤患者的5年生存率为100%，而pAKT阳性脊索瘤患者的5年生存率为45%。我们的研究结果证实，RTK经常改变脊索瘤。考虑到pAKT阳性的影响，RTK抑制剂可能是有效的，抑制AKT的药物，单独或与放疗联合，可能是难治性脊索瘤患者的有效治疗方法。(C)2013 Elsevier Inc. All rights reserved.
Chordomas are rare neoplasms arising from notochord remnants. Tyrosine kinase receptors (RTK) are altered in these lesions. We used a tissue microarray containing 58 chordomas to examine the expression of platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta, epidermal growth factor receptor (EGFR), c-Met, c-Kit, pAKT, mammalian target of rapamycin, and HER2 by immunohistochemistry and fluorescence in situ hybridization. Most tumors were positive for PDGFR-alpha (92%), PDGFR-beta (85%), c-Kit (77.4%), c-Met (96%), pAKT (82%), mammalian target of rapamycin (56%), HER2 (24%), and EGFR (26%) by immunohistochemistry. Amplifications or deletions could not be identified for HER2 or EGFR in the 13 cases available for fluorescence in situ hybridization analysis; however, chromosome 7 polysomy was detected in 29% of the cases. The only factor directly associated with a poorer survival rate was pAKT positivity (P = .042). The 5-year survival rate for patients with pAKT-negative chordomas was 100%, whereas it was 45% for patients with pAKT-positive chordomas. Our results confirm that RTKs are frequently altered in chordomas. Given the implications of pAKT positivity, RTK inhibitors might be efficacious, and drugs that inhibit AKT, alone or in combination with radiotherapy, could be an effective treatment for patients with refractory chordomas. (C) 2013 Elsevier Inc. All rights reserved.