title: Insulin-like growth factor II messenger ribonucleic acid expression in Wilms tumor, nephrogenic rest, and kidney.
abstract: BACKGROUND
  Wilms tumors (WTs) are embryonic neoplasms of the kidney that are believed to arise from primitive metanephrogenic blastema. Our previous reports and those of others indicate that WTs show an increased expression of insulin-like growth factor II (IGF-II) mRNA. However, the precise role of IGF-II on Wilms tumorigenesis is not known. A central question is to determine whether the increased IGF-II expression in WTs simply reflects the fetal nature of WTs (effect), or is induced by specific changes in gene expression (cause).
  
  
  METHODS
  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 shown in Table 1. In WTs, the relative area of blastemal, epithelial, poorly differentiated spindle cell and heterologous cell components were assessed. Dot and Northern blot hybridization, using cDNA probes, were done to assess the level of IGF-II mRNA expression. In situ RNA hybridization was employed to localize IGF-II transcripts. Immunohistochemistry was applied to frozen sections to demonstrate cytokeratin and type-IV collagen. These results were then correlated with the histology of WTs and their precursor lesions, i.e., nephrogenic rests (NRs).
  
  
  RESULTS
  Dot blot hybridization indicated that IGF-II transcripts were 32- to 64-fold more abundant in WTs than in the adjacent uninvolved kidneys. In situ hybridization showed that WTs, NRs, and fetal kidney shared a common feature in which IGF-II transcripts were predominantly associated with blastema. However, WTs and NRs differed from fetal kidney in that occasional epithelial structures and dense blastema showed aberrant, sustained IGF-II expression.
  
  
  CONCLUSIONS
  The data indicate two points. 1) There is an inverse correlation between nephroblastic differentiation 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.
authors.affiliation: Department of Pathology, University of Otago Medical School, Dunedin, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: Yun
authors.forename: A J
authors.initials: AJ
authors.lastname: Molenaar
authors.forename: A M
authors.initials: AM
authors.lastname: Fiedler
authors.forename: A J
authors.initials: AJ
authors.lastname: Mark
authors.forename: M R
authors.initials: MR
authors.lastname: Eccles
authors.forename: D M
authors.initials: DM
authors.lastname: Becroft
authors.forename: A E
authors.initials: AE
authors.lastname: Reeve
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002648:Child; D003094:Collagen / Q000032:analysis; D018240:Endodermal Sinus Tumor / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000502:physiology; D007633:Keratins / Q000032:analysis; D007668:Kidney / Q000737:chemistry* / Q000166:cytology / Q000196:embryology; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D013223:Statistics as Topic; D014158:Transcription, Genetic / Q000235:genetics; D015291:Transforming Growth Factors / Q000502:physiology; D009396:Wilms Tumor / Q000737:chemistry* / Q000235:genetics / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D007633:Keratins; D015291:Transforming Growth Factors; D003094:Collagen