Low expression of HLA-DRA, HLA-DPA1, and HLA-DPB1 is associated with poor prognosis in pediatric adrenocortical tumors (ACT)

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. Procedure This study analyzed the expression profile...

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Published in:	Pediatric blood & cancer Vol. 61; no. 11; pp. 1940 - 1948
Main Authors:	Leite, Fabíola A., Lira, Regia C. P., Fedatto, Paola F., Antonini, Sonir R. R., Martinelli Jr, Carlos E., de Castro, Margaret, Neder, Luciano, Ramalho, Leandra N. Z., Tucci Jr, Silvio, Mastelaro, Maria J., Seidinger, Ana L., Cardinalli, Izilda A., Yunes, José A., Brandalise, Silvia R., Tone, Luiz G., Scrideli, Carlos A.
Format:	Journal Article
Language:	English
Published:	United States Blackwell Publishing Ltd 01-11-2014 Wiley Subscription Services, Inc
Subjects:	Adolescent Adrenal Cortex Neoplasms - immunology Adrenal Cortex Neoplasms - mortality Adrenal Cortex Neoplasms - pathology adrenocortical tumors Child Child, Preschool children Female Hematology HLA class II HLA-DP alpha-Chains - analysis HLA-DP alpha-Chains - genetics HLA-DP beta-Chains - analysis HLA-DP beta-Chains - genetics HLA-DPA1 HLA-DR alpha-Chains - analysis HLA-DR alpha-Chains - genetics Humans Infant Male Medical prognosis Multivariate analysis Oncology Pediatrics Prognosis Tumors HLA class II adrenocortical tumors children prognosis HLA-DPA1
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Summary:	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. Procedure 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 cm3, 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. Conclusion 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. Pediatr Blood Cancer 2014;61:1940–1948. © 2014 Wiley Periodicals, Inc.
Bibliography:	Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) - No. 2010/7020-9 ark:/67375/WNG-BZ379ZZS-T ArticleID:PBC25118 istex:50913398FD420548A5BBE07FDEEB10E3E867A38B ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1545-5009 1545-5017
DOI:	10.1002/pbc.25118