title: Expression profile of apoptosis-related genes in childhood adrenocortical tumors: low level of expression of BCL2 and TNF genes suggests a poor prognosis.
abstract: BACKGROUND
  Impaired apoptosis has been implicated in the development of childhood adrenocortical tumors (ACT), although the expression of apoptosis-related gene expression in such tumors has not been reported.
  
  
  METHODS
  The mRNA expression levels of the genes CASP3, CASP8, CASP9, FAS, TNF, NFKB, and BCL2 were analyzed by quantitative real-time PCR in consecutive tumor samples obtained at diagnosis from 60 children with a diagnosis of ACT and in 11 non-neoplastic adrenal samples. BCL2 and TNF protein expression was analyzed by immunohistochemistry.
  
  
  RESULTS
  A significant association was observed between tumor size ≥100 g and lower expression levels of the BCL2 (P=0.03) and TNF (P=0.05) genes; between stage IV and lower expression levels of CASP3 (P=0.008), CASP9 (P=0.02), BCL2 (P=0.002), TNF (P=0.05), and NFKB (P=0.03); Weiss score ≥3 and lower expression of TNF (P=0.01); unfavorable event and higher expression values of CASP9 (P=0.01) and lower values of TNF (P=0.02); and death and lower expression of BCL2 (P=0.04). Underexpression of TNF was associated with lower event-free survival in uni- and multivariate analyses (P<0.01). Similar results were observed when patients with Weiss score <3 were excluded.
  
  
  CONCLUSIONS
  This study supports the participation of apoptosis-related genes in the biology and prognosis of childhood ACT and suggests the complex role of these genes in the pathogenesis of this tumor.
authors.affiliation: Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Cecília Fernandes
authors.initials: CF
authors.lastname: Lorea
authors.forename: Daniel Antunes
authors.initials: DA
authors.lastname: Moreno
authors.forename: Kleiton Silva
authors.initials: KS
authors.lastname: Borges
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Martinelli
authors.forename: Sonir Roberto Rauber
authors.initials: SR
authors.lastname: Antonini
authors.forename: Margaret
authors.initials: M
authors.lastname: de Castro
authors.forename: Silvio
authors.initials: S
authors.lastname: Tucci
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.forename: Leandra Naira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Izilda
authors.initials: I
authors.lastname: Cardinalli
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Seidinger
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Mastellaro
authors.forename: José Andres
authors.initials: JA
authors.lastname: Yunes
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Brandalise
authors.forename: Luiz Gonzaga
authors.initials: LG
authors.lastname: Tone
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Scrideli
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D017668:Age of Onset; D017209:Apoptosis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha