Endocrine Abstracts

Adrenocortical carcinomas (ACC) are rare and usually very aggressive tumors with heterogeneous outcomes. The individual variability in tumor progression and patients’ survival is linked to ACC biology and molecular heterogeneity, reinforcing the need to identify markers with prognosis value, to allow an accurate clinical strategy. Currently, in the absence of specific molecular markers, ACC prognosis is mainly predicted by the European Network for the Study of Adrenal Tumors (ENSAT) tumor stage and tumor proliferation index, assessed by Ki-67 immunohistochemistry. Glutaminolysis is one of the most studied metabolic processes in cancer metabolism context, since it plays a role in cell signaling transduction, proteins, and nucleotides biosynthesis, contributing to cell survival. Therefore, this study aimed to evaluate the role of glutaminolysis in ACC pathophysiology, and to estimate the potential usefulness of its molecular players for ACC prognosis. For that, the expression of proteins involved in glutaminolysis, namely glutaminase 2 (GLS2) and glutamate dehydrogenase 1 (GLUD1), was assessed by immunohistochemistry (IHC) in ACC (n=13) with different clinicopathological behaviors. The percentage of stained area for both molecular markers was quantified using the morphometric analysis tool, ImageJ. Positive staining for GLS2 and GLUD1 was observed in all ACC. Among these molecular markers, only GLS2 expression was positively correlated with ENSAT and Weiss scores. ACC with sinusoidal invasion presented higher GLS2 levels when compared to ACC without sinusoidal invasion. Additionally, GLS2 expression was associated with lower survival rates, whereas Ki-67 expression was not correlated with the survival of these patients. As conclusion, this study demonstrated that glutaminolysis seems to play a role in ACC tumor progression. Remarkably, GLS2 expression was linked with more aggressive malignant features, in particular advanced tumor stage and lower patients’ survival. Furthermore, in these cases, GLS2 showed to have a greater prognosis value when compared to the molecular marker currently used in clinical practice, Ki-67. To validate these data, a larger ACC cohort and mechanistic studies are needed.