Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.
Anatomical Pathology, NSW Heath Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Curr Protoc. 2021 Nov;1(11):e310. doi: 10.1002/cpz1.310.
Neuroblastoma, the most common extracranial solid tumor in young children, arises from the sympathetic nervous system. Our understanding of neuroblastoma has been improved by the development of both genetically engineered and xenograft mouse models of the disease. Anatomical pathology is an essential component of the phenotyping of mouse models of cancer, characterizing the morphologic effects of genetic manipulation and drug treatment. The Th-MYCN model, the most widely used of several genetically engineered mouse models of neuroblastoma, was established by targeted expression of the human MYCN gene to murine neural crest cells under the control of the rat tyrosine hydroxylase promoter. Neuroblastoma development in Th-MYCN mice is preceded by neuroblast hyperplasia-the persistence and proliferation of neural crest-derived neuroblasts within the sympathetic autonomic ganglia. The neuroblastomas that subsequently develop morphologically resemble human neuroblastoma and carry chromosomal gains and losses in regions syntenic with those observed in human tumors. In this overview, we describe the essential pathologic features for investigators when assessing mouse models of neuroblastoma. We outline human neuroblastoma as the foundation for understanding the murine disease, followed by details of the murine sympathetic ganglia from which neuroblastoma arises. Sympathetic ganglia, both with and without neuroblast hyperplasia, are described. The macroscopic and microscopic features of murine neuroblastoma are explained, including assessment of xenografts and tumors following drug treatment. An approach to experimental design is also detailed. Increased understanding of the pathology of murine neuroblastoma should improve reproducibility and comparability of research findings and assist investigators working with mouse models of neuroblastoma. © 2021 Wiley Periodicals LLC.
神经母细胞瘤是小儿最常见的颅外实体瘤，来源于交感神经系统。通过疾病的基因工程和异种移植小鼠模型的发展，我们对神经母细胞瘤的认识得到了提高。解剖病理学是癌症小鼠模型表型的重要组成部分，可描述遗传操作和药物治疗的形态学影响。Th-MYCN 模型是神经母细胞瘤几种基因工程小鼠模型中应用最广泛的模型，该模型通过靶向表达人类 MYCN 基因到鼠神经嵴细胞中，受大鼠酪氨酸羟化酶启动子的控制。Th-MYCN 小鼠中的神经母细胞瘤发生之前是神经母细胞增生 - 神经嵴来源的神经母细胞在交感自主神经节中的持续存在和增殖。随后发生的神经母细胞瘤在形态上类似于人类神经母细胞瘤，并携带与人类肿瘤中观察到的那些区域同源的染色体增益和丢失。在这篇综述中，我们描述了研究人员在评估神经母细胞瘤小鼠模型时评估小鼠模型的基本病理特征。我们将人类神经母细胞瘤作为理解小鼠疾病的基础，随后详细介绍了神经母细胞瘤起源的鼠交感神经节。描述了有和没有神经母细胞增生的交感神经节。解释了鼠神经母细胞瘤的宏观和微观特征，包括异种移植和药物治疗后的肿瘤评估。还详细介绍了实验设计的方法。对鼠神经母细胞瘤病理学的深入了解应提高研究结果的重现性和可比性，并协助使用神经母细胞瘤小鼠模型的研究人员。© 2021 Wiley Periodicals LLC.
