Ureteric Bud-derivatives in Wilms Tumor and Nephrogenic Rest

Abstract

Background/Aim: Recent studies suggest that not only the nephrogenic blastema but also the ureteric bud is involved in oncogenesis of Wilms' tumor (WT). However, the occurrence of ureteric bud (UB) derivatives in nephrogenic rest is not yet known. The aim of our study was to find UB derivatives in WT. Materials and Methods: Keratin 17 (KRT17) is expressed exclusively in UB in foetal kidneys. In this study KRT17 immunohistochemistry was used to detect UB-derivatives in 21 triphasic, 2 stromal and 3 epithelial predominant WTs and 9 nephrogenic rests. Results: We have detected KRT17 positive tubular structures resembling UB in 3 of 9 nephrogenic rests and 15 of 26 WTs. Conclusion: Not only the metanephric blastema but also the UB is involved in the histogenesis of nephrogenic rest and WT.Wilms' tumor (WT) or nephroblastoma is suggested to develop from maturation-arrested nephrogenic blastemal cells (1, 2). However, in triphasic WTs the presence of ureteric bud (UB)-like tubular structures surrounded by blastemal cells appear to indicate the involvement of UB or UB-derivatives in the development of WTs (3). A recent global gene expression analysis uncovered genes expressed in distinct compartments of the developing kidney as well as in WT (4). The presence of UB-like epithelial structures in WT has been confirmed by immunohistochemistry (3,4). Recently, we showed that KRT17 expression is restricted to cells of the UB in foetal kidneys and, therefore, it can be used as biomarker to detect UB derivatives (5). To obtain more information on the involvement of UB in the histogenesis of WT and its precursor lesions, we analysed the expression of KRT17 in WTs and accompanying nephrogenic rests by immunohistochemistry.

Novel concept of Wilms’ tumor development: involvement of pluripotential cells of ureteric bud

“…Data from the literature as well as from the present study demonstrate the occurrance of UBT derivatives in NR and WT [8,10,11]. These findings indicate that not only MMderived cells but also bipotential cells of UBT are involved in the development of NR and WT.…”

“…Considering the large number of nephrons, an error in the regulation of complex patterning may easily occur. Some of the differentiation arrested cells or cell groups may develop NR and later WT, both containing MM-and UBT-derived cells [8,10,11]. The UBT is a cell reservoir, and the bipotential UBT cells can give rise to trunk cells as well as more tip cells for continuing the branching process [14,21].…”

“…Comparative gene expression analysis identified overlapping fingerprint of gene expression in developing human kidney and WT and detected UB-like epithelial structures in tumor tissue by immunohistochemistry [10]. Recently, UB derivatives were found in nephrogenic rest (NR) [11].…”