GLUT1 expression in pediatric adrenocortical tumors: a promising candidate to predict clinical behavior
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Céline Pinheiro1,2,3,4,*, Sara Granja1,2,*, Adhemar Longatto-Filho1,2,4,5, André M. Faria6, Maria C.B.V. Fragoso6,7, Silvana M. Lovisolo8, Murilo Bonatelli4, Ricardo F.A. Costa3, Antonio M. Lerário9, Madson Q. Almeida6,7, Fátima Baltazar1,2,* and Maria C.N. Zerbini10*
1Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
2ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, Portugal
3Barretos School of Health Sciences Dr. Paulo Prata – FACISB, São Paulo, Brazil
4Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
5Laboratory of Medical Investigation (LIM-14), School of Medicina, University of São Paulo, São Paulo, Brazil
6Unidade de Suprarrenal, Disciplina de Endocrinologia e Metabologia, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
7Instituto do Câncer do Estado de São Paulo - ICESP, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
8Hospital Universitário, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
9Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA
10Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
*These authors have contributed equally to this work
Céline Pinheiro, email: [email protected]
Keywords: pediatric adrenocortical tumors, metabolic reprogramming, monocarboxylate transporter, glucose transporter, Warburg effect
Received: September 07, 2016 Accepted: June 12, 2017 Published: July 10, 2017
Background: Discrimination between benign and malignant tumors is a challenging process in pediatric adrenocortical tumors. New insights in the metabolic profile of pediatric adrenocortical tumors may contribute to this distinction, predict prognosis, as well as identify new molecular targets for therapy. The aim of this work is to characterize the expression of the metabolism-related proteins MCT1, MCT2, MCT4, CD147, CD44, GLUT1 and CAIX in a series of pediatric adrenocortical tumors.
Methods: A total of 50 pediatric patients presenting adrenocortical tumors, including 41 clinically benign and 9 clinically malignant tumors, were included. Protein expression was evaluated using immunohistochemistry in samples arranged in tissue microarrays.
Results: The immunohistochemical analysis showed a significant increase in plasma membrane expression of GLUT1 in malignant lesions, when compared to benign lesions (p=0.004), being the expression of this protein associated with shorter overall and disease-free survival (p=0.004 and p=0.001, respectively). Although significant differences were not observed for proteins other than GLUT1, MCT1, MCT4 and CD147 were highly expressed in pediatric adrenocortical neoplasias (around 90%).
Conclusion: GLUT1 expression was differentially expressed in pediatric adrenocortical tumors, with higher expression in clinically malignant tumors, and associated with shorter survival, suggesting a metabolic remodeling towards a hyperglycolytic phenotype in this malignancy.
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