Departament of Pathology, Biological Science Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Departament of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
Oral Dis. 2019 May;25(4):1229-1233. doi: 10.1111/odi.13056. Epub 2019 Feb 27.
The establishment of animal models of xenotransplantation can contribute to the elucidation of the molecular pathogenesis of ameloblastic fibrodentinomas (AFD) and it also provides an opportunity for drug tests. We aimed to evaluate the possibility of AFD tumour growth in a patient-derived xenograft (PDX) model. In addition, we characterized the human tumour and the PDXs.
A sample of a recurrent AFD was obtained and two fragments were contralaterally implanted subcutaneously in an 8-week old female NUDE mouse. After 250 days, the PDXs were removed and submitted to histopathological and molecular analysis. Immunohistochemical reactions for Ki67 and the phosphorylated form of ERK1/2 were carried out in both, PDXs and human tumour, and the presence of BRAFV600E was assessed.
From day 135 onwards, the PDXs presented a growth peak and remained stable until day 250. Histopathologically, the PDXs presented the same features of the patient's tumour. Tumour cells exhibited Ki67 and pERK1/2 immunoexpression in the patient's tumour and PDX. The AFD was wild-type for BRAFV600E.
The PDX model recapitulated well the human tumour after a long implantation time, representing a possible model to study the AFD and other odontogenic tumours pathobiology.
建立异种移植动物模型有助于阐明成釉细胞瘤-纤维牙本质瘤(AFD)的分子发病机制,为药物测试提供机会。我们旨在评估 AFD 肿瘤在患者来源异种移植(PDX)模型中生长的可能性。此外,我们对人类肿瘤和 PDX 进行了特征描述。
从复发性 AFD 中获得样本,并将两个片段在 8 周大的雌性无胸腺裸鼠的对侧皮下植入。250 天后,取出 PDX 并进行组织病理学和分子分析。在 PDX 和人类肿瘤中进行 Ki67 和 ERK1/2 磷酸化形式的免疫组织化学反应,并评估 BRAFV600E 的存在。
从第 135 天开始,PDX 出现生长高峰,并一直稳定到第 250 天。组织病理学上,PDX 呈现出与患者肿瘤相同的特征。肿瘤细胞在患者肿瘤和 PDX 中均表现出 Ki67 和 pERK1/2 免疫表达。AFD 在 BRAFV600E 中为野生型。
PDX 模型在长时间植入后很好地重现了人类肿瘤,代表了研究 AFD 和其他牙源性肿瘤病理生物学的可能模型。