title: Subsets of very low risk Wilms tumor show distinctive gene expression, histologic, and clinical features.
abstract: OBJECTIVE
  Recent studies suggest that children <24 months with stage I favorable histology Wilms tumors <550 g [very low risk Wilms tumors (VLRWT)] have an excellent prognosis when treated with nephrectomy only, without adjuvant chemotherapy. The identification of risk categories within VLRWT may enable refinement of their definition and optimization of their therapy.
  
  
  METHODS
  To define biologically distinct subsets, global gene expression analysis was done on 39 VLRWT that passed all quality-control parameters and the clusters identified were validated in an independent set of 11 VLRWT. Validation of select differentially expressed genes was done with immunohistochemistry on a tissue microarray from 20 of 39 tumors. Loss of heterozygosity (LOH) for 11p15, 1p, and 16q was analyzed in 52 tumors using PCR.
  
  
  RESULTS
  Two distinctive clusters were identified. One cluster included 9 tumors with epithelial differentiated tubular histology, paucity of nephrogenic rests, lack of LOH for 1p, 16q, and 11p, absence of relapse, and a unique gene expression profile consistent with arrest following mesenchymal-to-epithelial transition. The second cluster included 13 tumors with mixed histology, intralobar nephrogenic rests, and decreased expression of WT1. Three of 6 relapses occurred in this cluster. Of 43 informative tumors, 11p LOH was present in 5 of 5 relapses and 11 of 38 nonrelapses.
  
  
  CONCLUSIONS
  Two subsets comprising a total of 56% of VLRWT are identified that have pathogenetic and molecular differences and apparent differences in risk for relapse. If these predictors can be prospectively validated, this would enable the refinement of clinical stratification and less arbitrary definition of VLRWT.
authors.affiliation: Departments of Pathology and Preventive Medicine, Northwestern University Feinberg School of Medicine and Robert H. Lurie Cancer Center, Chicago, Illinois, USA.
authors.forename: Simone T
authors.initials: ST
authors.lastname: Sredni
authors.forename: Samantha
authors.initials: S
authors.lastname: Gadd
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Norman
authors.initials: N
authors.lastname: Breslow
authors.forename: Paul
authors.initials: P
authors.lastname: Grundy
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Dome
authors.forename: Robert C
authors.initials: RC
authors.lastname: Shamberger
authors.forename: J Bruce
authors.initials: JB
authors.lastname: Beckwith
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perlman
mesh_terms: D002675:Child, Preschool; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011786:Quality Control; D012008:Recurrence; D012306:Risk; D025721:WT1 Proteins / Q000096:biosynthesis / Q000235:genetics; D009396:Wilms Tumor / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D025721:WT1 Proteins