Zhang Paul J, Weber Randal, Liang Ho-Hi, Pasha Teresa L, LiVolsi Virginia A
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
Arch Pathol Lab Med. 2003 Nov;127(11):1480-4. doi: 10.5858/2003-127-1480-GFARIJ.
Juvenile nasopharyngeal angiofibroma is a rare nasopharyngeal tumor that occurs exclusively in adolescent boys. It is a histologically benign but locally persistent growth of stromal and vascular tissue. Although male hormones and some growth factors, such as transforming growth factor beta1 (TGF-beta1), insulin-like growth factor II (IGF-II), and, lately, the proto-oncogene beta-catenin, have been implicated in the histogenesis of the tumor, the biologic signaling pathways that drive this peculiar fibrovascular proliferation are still nuclear.
To evaluate immunoexpressions of beta-catenin, c-Kit, p130Cas, TGF-beta3, bone morphogenic protein 4, nerve growth factor (NGF), and the IGF receptor (IGF-1R) in a series of juvenile nasopharyngeal angiofibromas and to compare to that of a group of nasal polyps.
A standard immunohistochemical technique was used on paraffin sections of 12 sporadic juvenile nasopharyngeal angiofibromas and 15 nasal polyps with microwave or steam antigen retrieval. Immunoreactivity was analyzed semiquantitatively in stromal cells and endothelial cells of each case.
The expressions of beta-catenin (nuclear), c-Kit (cytoplasmic), and NGF (cytoplasmic) were higher and more frequent in stromal cells of juvenile nasopharyngeal angiofibromas than those of nasal polyps. Both juvenile nasopharyngeal angiofibromas and nasal polyps showed similarly frequent and strong immunoreactivity for p130Cas and TGF-beta3 and weak immunoreactivity for bone morphogenic protein 4 in both stromal cells and endothelial cells. No IGF-1R immunoreactivity was detected in any case of either group.
Our results support the role of beta-catenin in juvenile nasopharyngeal angiofibromas and suggest a potential involvement of c-Kit and NGF signaling pathways in the juvenile nasopharyngeal angiofibromas. Although the biologic significance of c-Kit in juvenile nasopharyngeal angiofibromas has yet to be defined, the finding of frequent and high c-Kit expression might have therapeutic importance for patients with juvenile nasopharyngeal angiofibromas.
青少年鼻咽血管纤维瘤是一种罕见的鼻咽部肿瘤,仅发生于青春期男性。它是一种组织学上良性但局部持续生长的间质和血管组织。尽管雄激素和一些生长因子,如转化生长因子β1(TGF-β1)、胰岛素样生长因子II(IGF-II),以及最近发现的原癌基因β-连环蛋白,与该肿瘤的组织发生有关,但驱动这种特殊纤维血管增殖的生物信号通路仍不清楚。
评估β-连环蛋白、c-Kit、p130Cas、TGF-β3、骨形态发生蛋白4、神经生长因子(NGF)和IGF受体(IGF-1R)在一系列青少年鼻咽血管纤维瘤中的免疫表达,并与一组鼻息肉进行比较。
采用标准免疫组织化学技术,对12例散发性青少年鼻咽血管纤维瘤和15例鼻息肉的石蜡切片进行微波或蒸汽抗原修复。对每例标本的间质细胞和内皮细胞的免疫反应性进行半定量分析。
青少年鼻咽血管纤维瘤间质细胞中β-连环蛋白(细胞核)、c-Kit(细胞质)和NGF(细胞质)的表达高于且较鼻息肉更频繁。青少年鼻咽血管纤维瘤和鼻息肉在间质细胞和内皮细胞中对p130Cas和TGF-β3的免疫反应性频率和强度相似,对骨形态发生蛋白4的免疫反应性较弱。两组任何病例均未检测到IGF-1R免疫反应性。
我们的结果支持β-连环蛋白在青少年鼻咽血管纤维瘤中的作用,并提示c-Kit和NGF信号通路可能参与青少年鼻咽血管纤维瘤的发生。尽管c-Kit在青少年鼻咽血管纤维瘤中的生物学意义尚未明确,但c-Kit频繁且高表达的发现可能对青少年鼻咽血管纤维瘤患者具有治疗意义。