Fukuzawa Ryuji, Anaka Matthew R, Morison Ian M, Reeve Anthony E
Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Department of Pathology, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
PLoS One. 2017 Oct 17;12(10):e0186333. doi: 10.1371/journal.pone.0186333. eCollection 2017.
Wilms tumour (WT) is an embryonal tumour that recapitulates kidney development. The normal kidney is formed from two distinct embryological origins: the metanephric mesenchyme (MM) and the ureteric bud (UB). It is generally accepted that WT arises from precursor cells in the MM; however whether UB-equivalent structures participate in tumorigenesis is uncertain. To address the question of the involvement of UB, we assessed 55 Wilms tumours for the molecular features of MM and UB using gene expression profiling, immunohistochemsitry and immunofluorescence. Expression profiling primarily based on the Genitourinary Molecular Anatomy Project data identified molecular signatures of the UB and collecting duct as well as those of the proximal and distal tubules in the triphasic histology group. We performed immunolabeling for fetal kidneys and WTs. We focused on a central epithelial blastema pattern which is the characteristic of triphasic histology characterized by UB-like epithelial structures surrounded by MM and MM-derived epithelial structures, evoking the induction/aggregation phase of the developing kidney. The UB-like epithelial structures and surrounding MM and epithelial structures resembling early glomerular epithelium, proximal and distal tubules showed similar expression patterns to those of the developing kidney. These observations indicate WTs can arise from a precursor cell capable of generating the entire kidney, such as the cells of the intermediate mesoderm from which both the MM and UB are derived. Moreover, this provides an explanation for the variable histological features of mesenchymal to epithelial differentiation seen in WT.
肾母细胞瘤（WT）是一种重现肾脏发育过程的胚胎性肿瘤。正常肾脏由两个不同的胚胎学起源形成：后肾间充质（MM）和输尿管芽（UB）。一般认为WT起源于MM中的前体细胞；然而，UB等效结构是否参与肿瘤发生尚不确定。为了解决UB是否参与其中的问题，我们使用基因表达谱分析、免疫组织化学和免疫荧光技术，评估了55例肾母细胞瘤的MM和UB分子特征。基于泌尿生殖系统分子解剖学项目数据的表达谱分析，确定了三相组织学组中UB和集合管以及近端和远端小管的分子特征。我们对胎儿肾脏和WT进行了免疫标记。我们关注一种中央上皮胚芽模式，这是三相组织学的特征，其特点是由MM和MM衍生的上皮结构包围的UB样上皮结构，让人联想到发育中肾脏的诱导/聚集阶段。UB样上皮结构以及周围的MM和类似于早期肾小球上皮、近端和远端小管的上皮结构，与发育中肾脏的表达模式相似。这些观察结果表明，WT可能起源于能够生成整个肾脏的前体细胞，例如MM和UB均从中衍生的中间中胚层细胞。此外，这也解释了WT中所见的间充质向上皮分化的可变组织学特征。
