Department of Pediatric Oncology, VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
Neuropathol Appl Neurobiol. 2013 Jun;39(4):426-36. doi: 10.1111/j.1365-2990.2012.01294.x.
Diffuse intrinsic pontine glioma (DIPG) is a fatal paediatric malignancy. Tumour resection is not possible without serious morbidity and biopsies are rarely performed. The resulting lack of primary DIPG material has made preclinical research practically impossible and has hindered the development of new therapies for this disease. The aim of the current study was to address the lack of primary DIPG material and preclinical models by developing a multi-institutional autopsy protocol.
An autopsy protocol was implemented in the Netherlands to obtain tumour material within a brief post mortem interval. A team of neuropathologists and researchers was available at any time to perform the autopsy and process the material harvested. Whole brain autopsy was performed and primary DIPG material and healthy tissue were collected from all affected brain areas. Finally, the study included systematic evaluation by parents.
Five autopsies were performed. The mean time interval between death and time of autopsy was 3 h (range 2-4). All tumours were graded as glioblastoma. None of the parents regretted their choice to participate, and they all derived comfort in donating tissue of their child in the hope to help future DIPG patients. In addition, we developed and characterized one of the first DIPG cell cultures from post mortem material.
Here we show that obtaining post mortem DIPG tumour tissue for research purposes is feasible with short delay, and that the autopsy procedure is satisfying for participating parents and can be suitable for the development of preclinical DIPG models.
弥漫性内在脑桥神经胶质瘤(DIPG)是一种致命的儿科恶性肿瘤。如果不造成严重的发病率,肿瘤切除术是不可能的,而且很少进行活检。因此,缺乏原发性 DIPG 材料使得临床前研究几乎不可能进行,并阻碍了这种疾病新疗法的发展。本研究的目的是通过开发多机构尸检协议来解决原发性 DIPG 材料和临床前模型的缺乏问题。
在荷兰实施了一项尸检协议,以在短时间的死后间隔内获得肿瘤材料。神经病理学家和研究人员团队随时可用,以进行尸检和处理收获的材料。进行全脑尸检,并从所有受影响的脑区收集原发性 DIPG 材料和健康组织。最后,该研究包括家长的系统评估。
进行了 5 次尸检。死亡和尸检时间之间的平均时间间隔为 3 小时(范围为 2-4 小时)。所有肿瘤均分级为胶质母细胞瘤。没有一位家长后悔选择参与,他们都希望通过捐献孩子的组织来帮助未来的 DIPG 患者,从而获得安慰。此外,我们还从死后材料中开发并鉴定了首批 DIPG 细胞培养物之一。
我们表明,在短时间延迟的情况下,从尸检中获得用于研究目的的 DIPG 肿瘤组织是可行的,尸检程序令参与的家长感到满意,并且可以适合开发临床前 DIPG 模型。