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用于1型神经纤维瘤病猪模型前瞻性研究的免疫组织化学标志物

Immunohistochemical Markers for Prospective Studies in Neurofibromatosis-1 Porcine Models.

作者信息

Meyerholz David K, Ofori-Amanfo Georgina K, Leidinger Mariah R, Goeken J Adam, Khanna Rajesh, Sieren Jessica C, Darbro Benjamin W, Quelle Dawn E, Weimer Jill M

机构信息

Department of Pathology.

University of Iowa, Iowa City, Iowa, Departments of Pharmacology and Anesthesiology, College of Medicine, University of Arizona, Tucson, Arizona.

出版信息

J Histochem Cytochem. 2017 Oct;65(10):607-618. doi: 10.1369/0022155417729357. Epub 2017 Aug 28.

Abstract

Neurofibromatosis type 1 (NF1) is a common, cancer-predisposing disease caused by mutations in the NF1 tumor gene. Patients with NF1 have an increased risk for benign and malignant tumors of the nervous system (e.g., neurofibromas, malignant peripheral nerve sheath tumors, gliomas) and other tissues (e.g., leukemias, rhabdomyosarcoma, etc.) as well as increased susceptibility to learning disabilities, chronic pain/migraines, hypertension, pigmentary changes, and developmental lesions (e.g., tibial pseudoarthrosis). Pigs are an attractive and upcoming animal model for future NF1 studies, but a potential limitation to porcine model research has been the lack of validated reagents for direct translational study to humans. To address that issue, we used formalin-fixed tissues (human and pigs) to evaluate select immunohistochemical markers (activated caspase-3, allograft inflammatory factor-1, beta-tubulin III, calbindin D, CD13, CD20, desmin, epithelial membrane antigen, glial fibrillary acidic protein, glucose transporter-1, laminin, myelin basic protein, myoglobin, proliferating cell nuclear antigen, S100, vimentin, and von Willebrand factor). The markers were validated by comparing known expression and localization in human and pig tissues. Validation of these markers on fixed tissues will facilitate prospective immunohistochemical studies of NF1 pigs, as well as other pig models, in a more efficient, reproducible, and translationally relevant manner.

摘要

1型神经纤维瘤病(NF1)是一种常见的、具有癌症易感性的疾病,由NF1肿瘤基因突变引起。NF1患者患神经系统(如神经纤维瘤、恶性外周神经鞘瘤、胶质瘤)和其他组织(如白血病、横纹肌肉瘤等)的良性和恶性肿瘤的风险增加,同时对学习障碍、慢性疼痛/偏头痛、高血压、色素沉着变化和发育性病变(如胫骨假关节)的易感性也增加。猪是未来NF1研究中一种有吸引力且新兴的动物模型,但猪模型研究的一个潜在限制是缺乏用于直接转化为人类研究的经过验证的试剂。为了解决这个问题,我们使用福尔马林固定组织(人类和猪)来评估选定的免疫组织化学标志物(活化的半胱天冬酶-3、同种异体移植炎症因子-1、β-微管蛋白III、钙结合蛋白D、CD13、CD20、结蛋白、上皮膜抗原、胶质纤维酸性蛋白、葡萄糖转运蛋白-1、层粘连蛋白、髓鞘碱性蛋白、肌红蛋白、增殖细胞核抗原、S100、波形蛋白和血管性血友病因子)。通过比较人类和猪组织中已知的表达和定位来验证这些标志物。在固定组织上对这些标志物进行验证将有助于以更高效、可重复且与转化相关的方式对NF1猪以及其他猪模型进行前瞻性免疫组织化学研究。

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