title: Steroidogenic factor 1 overexpression and gene amplification are more frequent in adrenocortical tumors from children than from adults.
abstract: BACKGROUND
  Steroidogenic factor 1 (SF-1) is a key determinant of endocrine development and function of adrenal cortex. SF-1 overexpression and gene amplification were previously demonstrated in a small group of pediatric adrenocortical tumors.
  
  
  OBJECTIVE
  Our objective was to determine the frequency of SF-1 protein expression and gene amplification in a large cohort of pediatric and adult adrenocortical tumors.
  
  
  METHODS
  SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults, whereas gene amplification was studied in 38 adrenocortical tumors (17 from children).
  
  
  METHODS
  Tissue microarray, multiplex ligation-dependent probe amplification, and quantitative real-time PCR were used.
  
  
  RESULTS
  A strong nuclear SF-1 expression was detected by tissue microarray in 56% (20 of 36) and 19% (13 of 67) of the pediatric and adult adrenocortical tumors, respectively (P = 0.0004). Increased SF-1 copy number was identified in 47% (eight of 17) and 10% (two of 21) of the pediatric and adult adrenocortical tumors, respectively (P = 0.02). All adrenocortical tumors with SF-1 gene amplification showed a strong SF-1 staining, whereas most of the tumors (61%) without SF-1 amplification displayed a weak or negative staining (P = 0.0008). Interestingly, a strong SF-1 staining was identified in five (29%) pediatric adrenocortical tumors without SF-1 amplification. The frequency of SF-1 overexpression and gene amplification was similar in adrenocortical adenomas and carcinomas.
  
  
  CONCLUSIONS
  We demonstrated a higher frequency of SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento e Laboratório de Hormônios e Genética Molecular (Laboratório de Investigação Médica 42), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 155, 20 andar Bloco 6, 05403-900 São Paulo, SP, Brasil. madsonalmeida@usp.br
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.forename: Ibere Cauduro
authors.initials: IC
authors.lastname: Soares
authors.forename: Tamaya C
authors.initials: TC
authors.lastname: Ribeiro
authors.forename: Maria Candida B V
authors.initials: MC
authors.lastname: Fragoso
authors.forename: Lidiane V
authors.initials: LV
authors.lastname: Marins
authors.forename: Alda
authors.initials: A
authors.lastname: Wakamatsu
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Ressio
authors.forename: Mirian Y
authors.initials: MY
authors.lastname: Nishi
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Lerario
authors.forename: Venancio A F
authors.initials: VA
authors.lastname: Alves
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D018246:Adrenocortical Adenoma / Q000235:genetics*; D018268:Adrenocortical Carcinoma / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054339:Steroidogenic Factor 1 / Q000235:genetics*; D046888:Tissue Array Analysis
chemical_list: D054339:Steroidogenic Factor 1