Endocrine Abstracts

The majority of adrenocortical tumors (ACT) are benign and hormonally non-functioning, in contrast to adrenocortical carcinomas (ACC), which are rare and usually very aggressive tumors. The differential diagnosis between these two entities is mainly based on unspecific and subjective criteria, contributing to the inaccuracy of diagnosis. Due to ACC molecular and biological heterogeneity, prognostic factors have a limited capacity to predict ACC clinical outcomes, leading to an inappropriate therapeutic strategy. Angiogenesis is a well-recognized hallmark of cancer. As a dynamic and a complex multistage mechanism, various signaling pathways regulate the growth and maintenance of blood vessels, such as the vascular endothelial growth factor (VEGF) and Ang-Tie pathways. This study aimed to evaluate the role of the VEGF and Ang-Tie pathways in ACT angiogenesis, in order to identify molecular markers that may contribute to the diagnosis and/or prognosis of ACC. The ACT studied included ACC (n=22), adrenocortical adenomas (ACA) with Cushing’s syndrome (n=8) and non-functioning ACA (n=13). For each sample, the expression of proteins involved in angiogenesis, namely CD34, VEGF, VEGF-R2, Ang1, Ang2, Tie1 and Tie2, were analyzed by immunohistochemistry. The percentage of the stained area for each protein was quantified using a morphometric analysis tool, except for VEGF. CD34, Ang1 and Ang2 expression was found to be significantly different between benign and malignant ACT. ACC presented lower CD34 expression when compared to ACA, whereas Ang1 and Ang2 expression was higher in ACC. Despite the differences observed, none of these proteins demonstrated to be accurate biomarkers for ACT differential diagnosis. Additionally, higher Tie1 expression was observed in ACC of patients with venous invasion and shorter overall survival. As conclusion, this study demonstrated for the first time that the Ang-Tie pathway has a role in ACC angiogenesis. The higher Ang2 levels in malignant ACT could be related with higher vascular permeability, and therefore facilitating tumor dissemination. In addition, the higher Tie1 expression in ACC patients with poor prognosis may represent a possible therapeutic target for ACC. Finding: This study was funded by the Foundation for Science and Technology (FCT) (PTDC/MEC-ONC/31384/2017).