Nonogaki Suely, Campos Heloisa G A, Butugan Ossamu, Soares Fernando A, Mangone Flávia Regina Rotea, Torloni Humberto, Brentani M Mitzi
Instituto Adolfo Lutz, Central, Divisão de Patologia, Laboratório de Imuno-histoquímica, CEP 01246-902;
Exp Ther Med. 2010 Nov;1(6):921-926. doi: 10.3892/etm.2010.141. Epub 2010 Aug 26.
Juvenile nasopharingeal angiofibroma (JNA) is a histologically benign locally aggressive tumor characterized by irregular vessels embedded in a fibrous stroma. Excessive vascularity results in bleeding complications, and the inhibition of angiogenesis is a promising strategy for managing extensive JNA tumors. To better characterize the endothelial components of JNA, we aimed to evaluate markers of vascular differentiation and proliferation, such as friend leukemia integration-1 (FLI-1) and endoglin, lymphatic markers, including podoplanin and vascular endothelial growth factor receptor 3 (VEGFR3) and its cognate ligand VEGFC, GLUT-1, a diagnostic marker that discriminates between hemangiomas and vascular malformations, and two markers of tissue remodeling, stromelysin 3 (ST3) and secreted acid protein rich in cysteine (SPARC). Antigens were assessed immunohistochemically in vessels and stromal cells of JNA archival cases (n=22). JNA endothelial cells were positive for endoglin, VEGFC and FLI-1, whereas podoplanin and VEGFR3 were negative in all cases. Both endothelial cells and fibroblasts stained for ST3 and SPARC. GLUT-1 was investigated in JNA cases, in infantile hemangiomas (n=123) and in vascular malformations (n=135) as controls. JNAs and vascular malformations were GLUT-1-negative, while hemangiomas showed positive staining. The presence of markers of endothelial differentiation and proliferation highlighted the hyper-proliferative state of JNA vessels. The absence of podoplanin and VEGFR3 underscores their blood endothelial cell characteristic. The absence of GLUT-1 discriminates JNAs from hemangiomas. ST3 and SPARC up-regulation in endothelial cells and fibroblasts may contribute to a compensatory signaling for controlling angiogenesis. Some of these markers may eventually serve as therapeutic targets. Our results may aid in the understanding of JNA pathophysiology.
青少年鼻咽血管纤维瘤（JNA）是一种组织学上为良性但具有局部侵袭性的肿瘤，其特征是纤维基质中嵌入不规则血管。血管过度增生会导致出血并发症，抑制血管生成是治疗广泛JNA肿瘤的一种有前景的策略。为了更好地表征JNA的内皮成分，我们旨在评估血管分化和增殖的标志物，如Friend白血病整合-1（FLI-1）和内皮糖蛋白，淋巴管标志物，包括血小板内皮细胞黏附分子-1和血管内皮生长因子受体3（VEGFR3）及其同源配体VEGFC，葡萄糖转运蛋白1（GLUT-1），一种区分血管瘤和血管畸形的诊断标志物，以及两种组织重塑标志物，基质溶解素3（ST3）和富含半胱氨酸的分泌酸性蛋白（SPARC）。通过免疫组织化学方法在JNA存档病例（n = 22）的血管和基质细胞中评估抗原。JNA内皮细胞内皮糖蛋白、VEGFC和FLI-1呈阳性，而血小板内皮细胞黏附分子-1和VEGFR3在所有病例中均为阴性。内皮细胞和成纤维细胞ST3和SPARC均呈染色阳性。在JNA病例、婴儿血管瘤（n = 123）和血管畸形（n = 135）作为对照中研究了GLUT-1。JNA和血管畸形GLUT-1呈阴性，而血管瘤呈阳性染色。内皮分化和增殖标志物的存在突出了JNA血管的高增殖状态。血小板内皮细胞黏附分子-1和VEGFR3的缺失强调了它们的血内皮细胞特征。GLUT-1的缺失将JNA与血管瘤区分开来。内皮细胞和成纤维细胞中ST3和SPARC的上调可能有助于控制血管生成的代偿信号。其中一些标志物最终可能成为治疗靶点。我们的结果可能有助于理解JNA的病理生理学。
