Epstein-Barr Virus Latent Membrane Protein 1 is not Associated with Vessel Density nor with Hypoxia Inducible Factor 1 Alpha Expression in Nasopharyngeal Carcinoma Tissue
Epstein-Barr Virus Latent Membrane Protein 1 is not Associated with Vessel Density nor with Hypoxia Inducible Factor 1 Alpha Expression in Nasopharyngeal Carcinoma Tissue
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DOI：
10.1007/s12105-009-0148-8
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发表时间：
2009-12-01
影响因子：
2.1
通讯作者：
Gulley, Margaret L.
中科院分区：
文献类型：
--
作者：
Benders, Alexander A.;Tang, Weihua;Gulley, Margaret L.
缺氧诱导因子-1 α（HIF-1 α）和缺氧诱导因子转录激活诱导的新血管生成因子可能通过诱导血管形成而促进肿瘤发生，血管形成反过来又提供氧气和营养物质促进肿瘤扩张。鼻咽癌（NPC）是一种几乎总是被EB病毒感染的侵袭性恶性肿瘤，其体外研究显示HIF-1 α被病毒潜伏膜蛋白1（LMP 1）上调。目前的研究使用免疫组织化学来检测HIF-1 α和LMP 1在自然感染的NPC组织中共表达的程度。采用免疫组织化学和灵敏的荧光和信号放大技术，优化分析程序，以在固定的组织切片中灵敏地定位HIF-1 α和LMP 1。通过CD 31免疫组织化学定量血管密度。LMP 1在所有18个NPC中均有局灶性表达，其中7/8个原位病变。与HIF-1a没有一致的共定位，HIF-1a通常仅在肿瘤细胞亚群中弱表达。LMP 1和HIF-1 α表达与血管密度无关，血管化程度在病例中差异很大。先进的免疫组化技术显示LMP 1在NPC中的表达比以前报道的更普遍。LMP 1与HIF-1 α表达或微血管程度之间没有一致的关系。血管密度的广泛变化的生物学基础值得进一步研究。
Hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the neo-angiogenic factors induced as a result of hypoxia inducible factor transcriptional activation may contribute to tumorigenesis by inducing vessel formation that in turn provides oxygen and nutrients promoting tumor expansion. In vitro studies of nasopharyngeal carcinoma (NPC), an aggressive malignancy that is nearly always infected by Epstein-Barr virus, show HIF-1 alpha is upregulated by viral latent membrane protein 1 (LMP1). The current study used immunohistochemistry to examine the extent to which HIF-1 alpha and LMP1 are co-expressed in naturally infected NPC tissues. Analytic procedures were optimized for sensitive localization of HIF-1 alpha and LMP1 in fixed tissue ections using immunohistochemistry with sensitive fluorescent and signal amplification technologies. Vessel density was quantified by CD31 immunohistochemistry. LMP1 was expressed focally in all 18 NPCs examined, including 7/8 in situ lesions. There was no consistent co-localization with HIF-1a which was usually only weakly expressed in a subset of neoplastic cells. Neither LMP1 nor HIF-1 alpha expression correlated with vessel density, and degree of vascularization varied widely among cases. Advanced immunohistochemical technologies reveal that LMP1 is expressed more commonly than previously reported in NPC. There is no consistent relationship between LMP1 and either HIF-1 alpha expression or degree of microvasculature. The biologic basis for the wide variation in vessel density deserves further investigation.