title: p53 accumulation in favorable-histology Wilms tumor is associated with angiogenesis and clinically aggressive disease.
abstract: OBJECTIVE
  Unfavorable histology (UH) in Wilms tumor has been linked to malfunction of the p53 tumor suppressor gene, which regulates (1) the endogenous angiogenesis suppressor thrombospondin-1 (TSP-1) and (2) vascular endothelial growth factor (VEGF). The authors hypothesized that clinically aggressive favorable histology Wilms tumor (FH), like UH, but distinct from standard-risk FH disease, would display altered p53/TSP-1 function and upregulated angiogenesis.
  
  
  METHODS
  Three Wilms tumor specimens manifesting different histology and clinical behavior were obtained: clinically aggressive UH, clinically aggressive FH, and standard-risk FH disease. Xenografts were induced intrarenally in athymic mice. P53, TSP-1, and VEGF status and neovascularity were assessed in tumor tissues. Lungs were evaluated for metastasis.
  
  
  RESULTS
  Clinically aggressive FH Wilms tumor displayed progressive alteration in p53/TSP-1 status and upregulation of VEGF. Such alteration was observed in the UH tumor, but was absent from the standard-risk FH tumor. Xenografts from clinically aggressive tumors displayed brisk neoangiogenesis and yielded lung metastases.
  
  
  CONCLUSIONS
  This is the first report of altered p53/TSP-1 function in association with clinically aggressive behavior in FH Wilms tumor. These characteristics were not observed in parallel studies of a nonaggressive FH tumor. Loss of wild-type p53 function may contribute to disease progression in FH Wilms tumor, in part by upregulation of VEGF.
authors.affiliation: Divisions of Pediatric Surgery, Department of Pathology, College of Physicians and Surgeons, Columbia University and Children's Hospital of New York, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Huang
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Soffer
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Kim
authors.forename: Akiko
authors.initials: A
authors.lastname: Yokoi
authors.forename: James T
authors.initials: JT
authors.lastname: Moore
authors.forename: Kimberly W
authors.initials: KW
authors.lastname: McCrudden
authors.forename: Christina
authors.initials: C
authors.lastname: Manley
authors.forename: William
authors.initials: W
authors.lastname: Middlesworth
authors.forename: Kathleen
authors.initials: K
authors.lastname: O'Toole
authors.forename: Charles
authors.initials: C
authors.lastname: Stolar
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Yamashiro
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Kandel
mesh_terms: D000818:Animals; D016228:Endothelial Growth Factors / Q000032:analysis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000601:surgery; D007680:Kidney Neoplasms / Q000737:chemistry / Q000378:metabolism; D008175:Lung Neoplasms / Q000737:chemistry / Q000556:secondary; D008222:Lymphokines / Q000032:analysis / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology*; D016612:Paraffin Embedding; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019700:Thrombospondin 1 / Q000032:analysis / Q000502:physiology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009396:Wilms Tumor / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors