Coexpression of erythropoietin and its receptor in endolymphatic sac tumors
Coexpression of erythropoietin and its receptor in endolymphatic sac tumors
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DOI：
10.3171/jns.2005.103.2.0284
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发表时间：
2005-08-01
影响因子：
4.1
通讯作者：
Zhuang, ZP
中科院分区：
文献类型：
--
作者：
Vogel, TWA;Vortmeyer, AO;Zhuang, ZP
物体。VOD Hippel-Lindau(VHL)病是以特定器官的多个肿瘤为特征的疾病。肿瘤的起源细胞和特定器官分布的原因尚不清楚。内淋巴囊肿瘤(ELST)是与VHL病相关的病变之一。以往对VHL病相关血管母细胞瘤(HBs)和肾细胞癌(RCC)的研究数据表明，VHL基因缺陷导致促红细胞生成素(EPO)及其受体(EPO-R)共表达，促进肿瘤生长。作者研究了5名VHL生殖系突变患者的ELST。对五个Elst样本的分析显示，野生型等位基因丢失，这与克努森关于肿瘤发生的两次命中假说一致。所有5例ELST标本均进行了光镜和免疫组织化学分析。免疫组织化学检测发现EPO和EPO-R在5种肿瘤中均有共同表达，并经逆转录-聚合酶链式反应和Western印迹分析证实。EPO的表达可能是VHL基因缺失的结果，而EPO-R的同时共表达可能反映了肿瘤发生的一种发育机制。EST中EPO和EPO-R的共同表达，以及这些病变与其他VHL疾病相关肿瘤的形态和遗传学相似性，表明不同器官的VHL疾病相关肿瘤具有共同的发病途径。
Object. VOD Hippel-Lindau (VHL) disease is characterized by multiple tumors in specific organs. The cell of origin and the reason for the particular organ distribution of the tumors remains unknown. Endolymphatic sac tumor (ELST) is one of the lesions associated with VHL disease. Data from previous studies of VHL disease-associated hemangioblastomas (HBs) and renal cell carcinomas (RCCs) have indicated that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth.Methods. The authors studied ELSTs from five patients with VHL germline mutations. Analysis of the five ELST samples revealed loss of the wild-type allele, consistent with Knudson's two-hit hypothesis for tumorigenesis. All five ELST specimens were characterized microscopically and by immunohistochemical analysis. Coexpression of Epo and Epo-R was found in all five tumors on immunohistochemical studies and confirmed through reverse transcription-polymerase chain reaction and Western blot analysis.Conclusions. Expression of Epo appears to be a result of VHL gene deficiency, whereas the simultaneous coexpression of Epo-R may reflect a developmental mechanism of tumorigenesis. Coexpression of Epo and Epo-R in ELSTs together with the morphological and genetic similarities of these lesions with other VHL disease-associated tumors indicates that VHL disease-associated tumors in different organs share common pathogenetic pathways.