Abstract
BackgroundDiscrimination 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.MethodsA 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.ResultsThe 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%).ConclusionGLUT1 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.
Highlights
Adrenocortical tumors (ACTs) are common neoplasms with a prevalence higher than 3% in individuals older than 50 years, being the great majority of these tumors benign [1]
glucose transporter 1 (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
All 3 monocarboxylate transporters (MCTs) isoforms, as well as the chaperone CD147, were expressed at high frequency in the plasma membrane of most tumor samples and, for MCT4, the frequency of expression was higher in malignant than in benign tumors, with no statistical significance
Summary
Adrenocortical tumors (ACTs) are common neoplasms with a prevalence higher than 3% in individuals older than 50 years, being the great majority of these tumors benign [1]. Adrenocortical carcinoma is a very rare and aggressive event, with an estimated annual worldwide incidence of 0.7-2 new cases per million [2,3,4]. ACTs are an even more rare event, with an estimated annual worldwide incidence of 0.2-0.3 cases per million children younger than 15 years. One study validates the reliability of Wieneke’s scoring system in predicting malignancy in pediatric ACTs [12], the series was small (only 13 patients) and this system did not gain a great acceptance in the literature yet. 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
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