Su Min-Cheng, Huang Wan-Chen, Lien Huang-Chun
Department of Pathology, Min-Sheng General Hospital, Taoyuan, Taiwan.
APMIS. 2008 Sep;116(9):771-8. doi: 10.1111/j.1600-0463.2008.00914.x.
Wilms' tumor is the most common pediatric renal neoplasm, but its occurrence in adults is very rare. In contrast to pediatric Wilms' tumor (PWT), very little is known about the pathogenesis of adult Wilms' tumor (AWT). Despite there currently being no morphological difference between AWT and PWT, a cytogenetic study has suggested that the pathogenesis of AWT might be different from that of PWT. Although dysregulation of the Wnt pathway has been implicated in PWT, its role in AWT has never been investigated. To investigate the role of dysregulation of the Wnt pathway in AWT, tumor samples from 4 AWTs and 19 PWTs were surveyed for subcellular localization of beta-catenin by immunohistochemistry and potential mutation of the beta-catenin gene by sequencing. Nuclear translocation of beta-catenin was found in one out of four cases of AWT, but none of them carried mutation of the beta-catenin gene. By comparison, nuclear translocation for beta-catenin and mutation of the beta-catenin gene were present in 53% (10/19) and 15.8% (3/19) of PWTs, respectively. Of the three mutations identified, we found a novel mutation combining a silent mutation (TCT to TCC, Ser37Ser) and an in-frame six-base-pair deletion (del GGTGCC, del Gly38Ala39). This report suggests that dysregulation of the Wnt pathway might also play a role in the pathogenesis of AWT.
肾母细胞瘤是最常见的小儿肾肿瘤，但在成人中极为罕见。与小儿肾母细胞瘤（PWT）不同，人们对成人肾母细胞瘤（AWT）的发病机制知之甚少。尽管目前AWT和PWT在形态学上没有差异，但一项细胞遗传学研究表明，AWT的发病机制可能与PWT不同。虽然Wnt信号通路失调与PWT有关，但其在AWT中的作用从未被研究过。为了研究Wnt信号通路失调在AWT中的作用，通过免疫组织化学检测了4例AWT和19例PWT肿瘤样本中β-连环蛋白的亚细胞定位，并通过测序检测了β-连环蛋白基因的潜在突变。在4例AWT中有1例发现β-连环蛋白核易位，但均未携带β-连环蛋白基因突变。相比之下，PWT中β-连环蛋白核易位和β-连环蛋白基因突变分别占53%（10/19）和15.8%（3/19）。在鉴定出的三个突变中，我们发现了一个新的突变，它结合了一个沉默突变（TCT突变为TCC，Ser37Ser）和一个框内六碱基对缺失（del GGTGCC，del Gly38Ala39）。本报告表明，Wnt信号通路失调可能也在AWT的发病机制中起作用。
