INSULIN-LIKE GROWTH FACTOR-II MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN WILMS-TUMOR, NEPHROGENIC REST, AND KIDNEY

BACKGROUND: Wilms tumors (WTs) are embryonic neoplasms of the kidney t hat are believed to arise from primitive metanephrogenic blastema. Our previous reports and those of others indicate that WTs show an increa sed expression of insulin-like growth factor II (IGF-II) mRNA. However , the precise role of IGF-II on Wilms tumorigenesis is not known. A ce ntral question is to determine whether the increased IGF-II expression in WTs simply reflects the fetal nature of WTs (effect), or is induce d by specific changes in gene expression (cause). EXPERIMENTAL DESIGN: This study included 31 sporadic WTs, 7 fetal and 3 adult kidneys and 1 yolk sac tumor. Clinical and histologic summaries of WT cases are sh own in Table 1. In WTs, the relative area of blastemal, epithelial, po orly differentiated spindle cell and heterologous cell components were assessed. Dot and Northern blot hybridization, using cDNA probes, wer e done to assess the level of IGF-II mRNA expression. In situ RNA hybr idization was employed to localize IGF-II transcripts. Immunohistochem istry was applied to frozen sections to demonstrate cytokeratin and ty pe-IV collagen. These results were then correlated with the histology of WTs and their precursor lesions, i.e., nephrogenic rests (NRs). RES ULTS: Dot blot hybridization indicated that IGF-II transcripts were 32 - to 64-fold more abundant in WTs than in the adjacent uninvolved kidn eys. In situ hybridization showed that WTs, NRs, and fetal kidney shar ed a common feature in which IGF-II transcripts were predominantly ass ociated with blastema. However, WTs and NRs differed from fetal kidney in that occasional epithelial structures and dense blastema showed ab errant, sustained IGF-II expression. CONCLUSIONS: The data indicate tw o points. 1) There is an inverse correlation between nephroblastic dif ferentiation and IGF-II expression in developing fetal kidney. 2) The IGF-II expression in WTs and NRs does not simply reflect the embryonal nature of the tumor but is rather significantly altered, suggesting a role as a transforming growth factor in Wilms tumorigenesis.