Low Expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 is Associated With Poor Prognosis in Pediatric Adrenocortical Tumors (ACT)

BackgroundLow 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.ProcedureThis 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.ResultsA 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 200cm(3), tumor weight 100g, 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.ConclusionOur 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. Pediatr Blood Cancer 2014;61:1940-1948. (c) 2014 Wiley Periodicals, Inc.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Ribeirao Preto Med Sch, Dept Pediat, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Ribeirao Preto Med Sch, Dept Pathol, BR-14049900 Ribeirao Preto, SP, BrazilUniv São Paulo, Ribeirao Preto Med Sch, Dept Surg, BR-14049900 Ribeirao Preto, SP, BrazilUniv Estadual Campinas, Ctr Infantil Boldrini, Campinas, SP, BrazilFAPESP: 2010/7020-9Web of Scienc