The Epithelial Mesenchymal Transition Process in Wilms Tumor

免疫组织化学 威尔姆斯瘤 间充质干细胞 病理 转移 Wnt信号通路 上皮-间质转换 生物 组织学 组织微阵列 癌症研究 分子生物学 癌症 医学 细胞生物学 信号转导 遗传学
作者
Francisco Giner,Isidro Machado,Rosa Noguera,Eva Villamón,Antonio Pellı́n,Silvia Calabuig‐Fariñas,Amando Peydró-Olaya,Samuel Navarro,Antonio Llombart‐Bosch
出处
期刊:Applied Immunohistochemistry & Molecular Morphology 卷期号:19 (4): 369-375 被引量:3
标识
DOI:10.1097/pai.0b013e31820287a7
摘要

Background Until now, only a few mouse-transplanted human tumors or experimental Wilms tumor (WT) cell lines have been described. The aim of this study was to show the biological behavior, including histology, immunohistochemistry (IHC), and molecular biology, of a WT including the original tumor and metastasis transferred into nude mice and followed for successive generations in xenografts. Methods A WT metastasis was xenotransplanted into nude mice and the mice was monitored for 7 passages over a period of 29 months; the original neoplasm was comparatively studied. The morphology was evaluated by optical and electron microscopy. The protein expression was analyzed by immunohistochemistry in whole sections and in tissue microarray. The molecular studies were carried out by multiplex ligation-dependent probe amplification and polymerase chain reaction analysis. Results The histology changed markedly between the fourth and fifth transfer. The tumor exhibited an increased epithelial component (>40%) together with a slowing in the growth rate (8 mo). An epithelial-mesenchymal transition seemed to take place in the fourth passage and increased thereafter. The genetic studies also showed a WT5 deletion and a MYCN gain in all the tumor samples in passage 4 and beyond, but did not show E-cadherin, β-catenin, and APC mutations. Conclusions An epithelial pattern was associated with slow tumor growth, whereas the predominance of mesenchymal spindle cells with striated muscle cell differentiation was related with a high growth rate. The in vivo reorganization of the tumor components (blastemal, epithelial, and mesenchymal) does not seem to be related with the Wnt and EMT pathways.

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