title: SIX1 protein expression selectively identifies blastemal elements in Wilms tumor.
abstract: BACKGROUND
  Wilms tumor (WT) is the most common renal neoplasm in children. Histologically, most WTs consist of three tissue elements: blastema, epithelium, and stroma. Some cases also show diffuse or focal anaplastic features. Previous studies have shown that a predominance of blastemal cells in post-chemotherapy WT specimens is associated with a poor clinical course. However, there is currently no molecular marker for blastemal cells, and risk stratification for post-nephrectomy treatment is therefore often based on clinico-histological parameters alone.
  
  
  METHODS
  In the present study, three public gene expression microarray datasets, including 82 WTs and 8 normal fetal kidneys, were used to establish a consensus gene expression profile of WT. By bioinformatic analyses, 17 genes overexpressed in WT compared to fetal kidney were then selected for evaluation of their protein expression in WT cell lines and in the different histological components in paraffin-embedded WT tissue sections by immunofluorescence.
  
  
  RESULTS
  Most of the evaluated proteins were expressed in all three common histological components. A prominent exception was SIX1, being expressed predominantly in blastemal elements in 24/25 pediatric cases containing blastema. Anaplastic elements exhibited highly variable SIX1-positivity. The SIX2 protein, known to be co-expressed with SIX1 during nephrogenesis, only exhibited blastemal-predominant expression in half of the SIX2 evaluated cases.
  
  
  CONCLUSIONS
  Genes highly expressed in WT compared to fetal kidney are generally overexpressed in all of the three common WT tissue elements. An exception is the predominant expression of SIX1 in blastemal cells, hereby identifying this protein as a candidate marker for blastema.
authors.affiliation: Department of Clinical Genetics, Lund University, University and Regional Laboratories, Lund, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sehic
authors.forename: Jenny
authors.initials: J
authors.lastname: Karlsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Sandstedt
authors.forename: David
authors.initials: D
authors.lastname: Gisselsson
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009396:Wilms Tumor / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; C099236:SIX1 protein, human