title: Low expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 is associated with poor prognosis in pediatric adrenocortical tumors (ACT).
abstract: BACKGROUND
  Low expression of HLA class II antigens has been associated with more aggressive disease in several human malignancies including adult adrenocortical tumors (ACT), but their clinical relevance in pediatric ACT needs to be investigated.
  
  
  METHODS
  This study analyzed the expression profile of three class II histocompatibility genes (HLA-DRA, HLA-DPA1, and HLA-DPB1) in 58 consecutive pediatric ACT (13 adenomas and 45 carcinomas) by quantitative real time PCR and their association with clinical and biological features. HLA-DPA1 protein level was determined by immunohistochemistry.
  
  
  RESULTS
  A significant association (P < 0.01) was observed between lower expression levels of the three genes analyzed and poor prognostic factors such as age ≥ 4 years, tumor size ≥ 200 cm(3), tumor weight ≥ 100 g, and metastatic disease; the presence of an unfavorable event and death. Underexpression of the HLA-DRA, HLA-DPA1, and HLA-DPB1 genes were associated with lower 5-year event-free survival (EFS) (P = 0.017, P < 0.001, and P = 0.017, respectively). Cox multivariate analysis showed that HLA-DPA1 was an independent prognostic factor (P = 0.029) when analyzed in association with stage IV, age and tumor size. Significantly lower EFS was also observed in patients with negative/weak immunostaining for HLA-DPA1 (P = 0.002). Similar results were observed when only patients classified as having carcinomas were analyzed.
  
  
  CONCLUSIONS
  Our results suggest that lower expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 genes may contribute to more aggressive disease in pediatric ACT. HLA-DPA1 immunostaining may represent potential aggressiveness marker in this tumor.
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medicine School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Fabíola A
authors.initials: FA
authors.lastname: Leite
authors.forename: Regia C P
authors.initials: RC
authors.lastname: Lira
authors.forename: Paola F
authors.initials: PF
authors.lastname: Fedatto
authors.forename: Sonir R R
authors.initials: SR
authors.lastname: Antonini
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Martinelli
authors.forename: Margaret
authors.initials: M
authors.lastname: de Castro
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.forename: Leandra N Z
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Silvio
authors.initials: S
authors.lastname: Tucci
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Mastelaro
authors.forename: Ana L
authors.initials: AL
authors.lastname: Seidinger
authors.forename: Izilda A
authors.initials: IA
authors.lastname: Cardinalli
authors.forename: José A
authors.initials: JA
authors.lastname: Yunes
authors.forename: Silvia R
authors.initials: SR
authors.lastname: Brandalise
authors.forename: Luiz G
authors.initials: LG
authors.lastname: Tone
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Scrideli
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D059867:HLA-DP alpha-Chains / Q000032:analysis / Q000235:genetics*; D059868:HLA-DP beta-Chains / Q000032:analysis / Q000235:genetics*; D059805:HLA-DR alpha-Chains / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis
chemical_list: D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen; D059805:HLA-DR alpha-Chains
keywords: HLA class II; HLA-DPA1; adrenocortical tumors; children; prognosis